Medicine 2 Flashcards

Question

Anaemia screening before surgery

Answer 1

Anaemia is the most common abnormality seen in pre-op patients: <60 g/L will require transfusion <100 g/L may require transfusion depending on cardiac risk and anticipated blood loss.

Answer 2

= a malignant clonal proliferation of plasma cells (derived from B-lymphocytes). Normally, many different plasma cells produce a range of immunoglobulins – i.e. they are polyclonal. In myeloma, a single clone of plasma cells produces a single immunoglobulin. => When you measure the immunoglobulins in a patient with myeloma, one of the type of antibody will be significantly abundant

Answer 3

Older age (average age of presentation is 70) Black African ethnicity FHx Obesity

Answer 4

“CRAB” – calcium, renal, anaemia, bone: Osteolytic bone lesions (due to osteoclast activation) => Backache, pathological fractures, hypercalcaemia (bones, stones, moans and groans) Bone marrow failure => Infection, symptoms of anaemia, bleeding Renal impairment => Seen in 20% at diagnosis, due to light chain deposition

Answer 5

Hypercalcaemia, Spinal cord compression, Hyper-viscosity, Acute renal failure.

Answer 6

FBC – normochromic normocytic anaemia; leucopaenia Blood film – rouleaux formation ESR – raised U&Es – often deranged Calcium – raised ALP – normal Serum/urine electrophoresis => Paraprotein monoclonal band seen Urine Bence-Jones protein – positive Skeletal XR => Punched out lytic lesions Bone marrow biopsy => Increased clonal plasma cells >10% => If under 10%, may be termed “monoclonal gammopathy of uncertain significance” (MGUS)

Answer 7

- Supportive therapy - Chemotherapy - Radiotherapy - Bone marrow stem cell transplants used if <70

Answer 8

The original myeloma cell is very resistant, so often returns. Median survival is 3-4 years. Death is usually from renal failure/infection.

Answer 9

= malignant proliferation of lymphocytes. Most commonly accumulate in peripheral lymph nodes, but can accumulate in the peripheral blood or infiltrate organs. Most are derived from B cells. Classified as Hodgkin's or Non-Hodgkin's

Answer 10

Characterised by Reed-Sternberg cells => Binucleate “mirror cells” on biopsy. Largest peak of incidence is young adults (20-35 years) Second peak in 50-70-year olds. Disease is slow growing, usually localised and rarely fatal.

Answer 11

- Affected sibling - HIV, EBV - Autoimmune conditions – e.g. SLE, RA - FHx

Answer 12

Enlarged, non-tender, “rubbery” lymph nodes (typically cervical) Fatigue, itching 25% will have B-symptoms, with profuse night sweats. For some patients, alcohol can induce lymph node pain Mediastinal lymph nodes can have mass effects (SVC/bronchial obstruction) O/E: - Lymphadenopathy - Hepatosplenomegaly in 50% - Potentially signs of cachexia/anaemia

Answer 13

Includes all lymphomas without the presence of Reed-Sternberg cells. Peak incidence = 70 years Can be further classes into high/low grade => HIGH grade – divide rapidly, typically present with rapid onset lymphadenopathy; more aggressive but better prognosis if identified and treated. => LOW grade – divide slowly, typically present more insidiously and thus tend to be widely disseminated at diagnosis, often incurable.

Answer 14

Nodal disease – 75% have superficial lymphadenopathy Extra-nodal disease – oropharynx, skin, CNS, gut, lung B-symptoms – weight loss indicates disseminated disease. Bone marrow failure Presentation is similar to Hodgkin’s lymphoma and often they can only be differentiated when the lymph node is biopsied.

Answer 15

FBC, U&E, LFT, ESR, blood film, Ca2+ LDH => Often raised in Hodgkin’s lymphoma but is not specific and can be raised in other cancers and many non-cancerous diseases. Lymph node biopsy is the key diagnostic test. => Reed-Sternberg cells in Hodgkin’s Lymphoma Staging CT/MRI/PET

Answer 16

The staging system used for both Hodgkins and non-Hodgkins lymphoma. The system puts importance on whether the affected nodes are above or below the diaphragm. Stage 1: Confined to one region of lymph nodes. Stage 2: In more than one region but on the same side of the diaphragm (either above or below). Stage 3: Affects lymph nodes both above and below the diaphragm. Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.

Answer 17

HODGKIN'S - Chemotherapy - Radiotherapy - Chemo-radiotherapy NON-HODGKIN'S Involves a combination of treatments depending on the type and staging of the lymphoma: - Watchful waiting - Chemotherapy - Monoclonal antibodies such as rituximab - Radiotherapy - Stem cell transplantation

Answer 18

Blood film => Hyper segmented neutrophils in B12/folate deficiency LFTs / TFTs => ?Thyroid / hepatic cause => Raised bilirubin in B12/folate deficiency Serum B12 and folate levels If B12 low: - Anti-parietal cell antibodies - Anti-intrinsic factor antibodies - Schilling test Bone marrow biopsy:  Megaloblasts suggest B12/folate deficiency (also seen in myelodysplasia)  Deoxyuridine suppression test – can be used to differentiate B12/folate deficiency in vitro after bone marrow biopsy.

Answer 19

Serum folate reflects recent intake, so many labs do red cell folate.

Answer 20

distinguishes between pernicious anaemia and small bowel disease Radiolabelled B12 given with and without IF The amount of labelled B12 excreted in the urine then detected.

Answer 21

B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate. Activated folate is required for DNA synthesis, and thus if there is a deficiency in either B12 or folate, DNA synthesis malfunctions. In this case, the DNA fails to stop erythrocyte development, leading to very large cells, which are eventually trapped and destroyed in the reticulo-endothelial system.

Answer 22

Intrinsic factor is secreted by gastric parietal cells, and binds free B12. Receptors for the IF-B12 complex are present on the brush border of the terminal ileum, where B12 is absorbed. IF is generally necessary for B12 ingestion, but even in its complete absence, around 2% of B12 can still be absorbed.

Answer 23

Humans rely on animal sources of B12 – e.g. meat, fish, eggs and milk. The liver contains very large stores of B12 => It is secreted in bile but most of this is normally reabsorbed.

Answer 24

high dose PO B12 supplementation can be enough to treat pernicious anaemia (as ~2% can still be absorbed in the abscence of IF) Initially patients are often treated with IM B12 on alternate days before switching to PO for maintenance

Answer 25

Chronic low dietary intake – vegans Impaired binding in the stomach – pernicious anaemia, congenital absence of IF, gastrectomy. Small bowel disease – resection, Crohn’s/backwash ileitis in UC, bacterial overgrowth. (Pancreatitis, coeliac disease and metformin can all cause mild impairment of B12 absorption, but not enough to cause significant B12 deficiency. )

Answer 26

= Autoimmune disease, resulting in severe B12 deficiency There are 3 autoantibodies that may contribute towards disease: 1. Autoantibodies against parietal cells 2. Blocking antibodies - Prevent IF-B12 binding - Most common abnormality 3. Binding antibodies: - Prevent IF binding to ileal receptors

Answer 27

Simultaneous dorsal column and corticospinal tract loss due to B12 deficiency => Gives a combination of UMN and LMN signs. Initial presentation is with peripheral neuropathy O/E there is classical triad of extensor plantars, brisk knee jerk reflex but absent ankle jerk reflex => Tone and power usually normal => Gait may be ataxic

Answer 28

Folate (folic acid monoglutamate) is not itself present in nature, but occurs as polyglutamates dihydrofolate (DHF) or tetrahydrofolate (THF) These are found in green vegetables and offal (however cooking causes a loss of up to 90% of the folate). DHF and THF are converted to folate in the upper GI tract, and folate is absorbed in the jejunum

Answer 29

Poor nutritional intake – poor diet, alcohol excess, anorexia. Malabsorption – coeliac disease Anti-folate drugs – trimethoprim, methotrexate, anti-convulsants Excess physiological use – pregnancy, lactation, prematurity. Excess pathological use – excess erythrocyte production, malignancy, inflammatory diseases

Answer 30

Folic acid 5 mg/day PO for 4 months Always combined with B12, unless the patient is known to have normal B12 levels.

Answer 31

Is there acute blood loss? Is there underlying chronic disease? Is it haemolytic? Are other cell lines affected (i.e. bone marrow failure)?

Answer 32

Normochromic or hypochromic, rarely severe. Seen in chronic infection, malignancy, CKD, rheumatoid disorders. Pathology involves predominant WBC production in the bone marrow. Low serum iron, raised ferritin, low TIBC, normal STR.

Answer 33

Hb, reticulocytes, WBC and platelets all equally low. There will be alterations on the blood film These patients require bone marrow biopsy. No abnormal blasts in pancytopaenic marrow = aplastic anaemia (idiopathic or due to drugs). Other causes will be apparent on marrow examination => E.g. haematological malignancies, metastatic disease, myelofibrosis, myelodysplasia. Parvovirus infection can also cause cessation of marrow erythropoiesis.

Answer 34

A group of disorders including – myelofibrosis, polycythaemia rubra vera, and essential thrombocytosis. Clones of haematopoietic stem cells proliferate in the marrow, yet retain the ability to differentiate. Considered PRE-LEUKAEMIC.

Answer 35

Clonal proliferation of megakaryocytes, leading to persistently raised platelets => This is often asymptomatic => The platelets have abnormal function Symptoms: => The most common presentation is microvascular occlusion. => Other symptoms may be related to bleeding or arterial/venous thrombosis.

Answer 36

= Malignant proliferation of a clone derived from one pluripotent marrow cell. Excess production of RBCs, WBCs and platelets lead to serum hyper-viscosity and thrombotic complications. Presentation: - Often asymptomatic - Arterial/venous thrombosis - Rarer – vague hyperviscosity symptoms (headache, dizziness, tinnitus, facial swelling, burning sensation in fingers/toes; splenomegaly; gout.

Answer 37

Diagnosis: - Increased red cell mass - Ix for JAK2 mutation (PCV cells often carry activating mutation in the tyrosine kinase (JAK2) gene) Key differentials to r/o = hypoxia and renal disease (in these secondary PCV’s only the RBCs are raised). Treatment: - Repeated venesection - Low dose aspirin

Answer 38

= Hyperplasia of megakaryocytes, which produce excess platelet-derived growth factor, leading to marrow fibrosis and metaplasia. There is secondary haematopoiesis in the liver/spleen, leading to massive hepatosplenomegaly (= most common presentation). Symptoms: - B symptoms - Abdominal discomfort - Sx of bone marrow failure Essential thrombocytopaenia and PCV both may progress to myelofibrosis or AML, yet the risk is relatively rare.

Answer 39

= A rare stem cell disorder leading to pancytopenia and hypoplastic bone marrow. Most commonly autoimmune Triggered by drugs, viruses or irradiation. Can be inherited (Fanconi anaemia) Symptoms are of bone marrow failure Diagnosis is with bone marrow biopsy.

Answer 40

Blood product transfusion Immunosuppression in autoimmune conditions In younger patients, allogenic bone marrow transplant may be curative.

Answer 41

= the breakdown of RBCs before the end of their normal lifespan (120 days). Can be: 1. Intravascular 2. Extravascular (reticuloendothelial system of the liver, spleen and bone marrow). This may be asymptomatic, but haemolytic anaemia develops if the bone marrow does not sufficiently compensate.

Answer 42

INTRINSIC Haemoglobinopathies – e.g. sickle cell/thalassaemias Membranopathies – spherocytosis/elliptocytosis Enzymeopathies – G6PD/PK deficiency EXTRINSIC Autoimmune disease Alloimmune disease – transfusion/transplant reaction, rhesus disease Drug-induced – e.g. penicillins Infection – malaria and some other parasites Microangiopathic haemolytic anaemias – e.g. DIC

Answer 43

Signs suggestive of increased RBC breakdown: - Anaemia with raised MCV - Raised bilirubin – unconjugated, pre-hepatic jaundice - Raised serum LDH (gets released from RBCs) Signs suggestive of increased RBC production: - Raised reticulocyte count BLOOD FILM can give clues as to the cause Further tests: - Coomb’s test (DAT) = Identifies RBCs coated with antibodies or complement, indicating an immune cause of haemolysis. - Hb electrophoresis = Can identify different haemoglobinopathies - Enzyme assays = If other causes have been excluded

Answer 44

Hypochromic, microcytic cells – thalassaemia Sickle cells – SCA Spherocytes – hereditary spherocytosis or autoimmune haemolytic anaemia Elliptocytes – hereditary elliptocytosis Heinz bodies / “bite” cells – G6PD deficiency Schistocytes – microangiopathic haemolytic anaemia

Answer 45

X-linked inheritance => More common in African and Mediterranean males (females will have mild symptoms). Presentation: - Mostly asymptomatic, but susceptible to oxidative crises due to reduced glutathione production. - These attacks cause rapid anaemia and jaundice with “bite cells” and “blister cells” seen on the blood film. Attacks may be precipitated by drugs (aspirin, primaquine, sulphonamides), broad bean consumption or illness.

Answer 46

Diagnosis is with enzyme assay 3 months after initial crisis BITE CELLS on blood film Tx: - Precipitant avoidance (e.g. broad beans) - Transfusion if severe - Splenectomy may help with chronic haemolysis

Answer 47

Autosomal recessive condition Reduced ATP production, shortening the lifespan of RBCs Homozygotes usually present with neonatal jaundice and later chronic jaundice with hepatosplenomegaly.

Answer 48

Dx = enzyme assay Tx = Often well tolerated and no specific therapy is needed, although splenectomy may help.

Answer 49

Autosomal dominant membrane defect => Leading to spherical RBCs These are less deformable, thus can become trapped in the spleen => leads to haemolysis, splenomegaly and jaundice.

Answer 50

Autosomal dominant defect => "elliptocytes" Mostly asymptomatic

Answer 51

Both are treated with folate. Splenectomy is curative, but reserved for severe disease.

Answer 52

= Autosomal recessive disorder Causes abnormal production of beta-globulin chains, due to a single amino acid substitution (glu6val) This results in the production of HbS rather than HbA Much more common in patients of African origin There are two genotypes: - HbSS – sickle cell anaemia phenotype - HbAS – sickle cell trait

Answer 53

= Autosomal recessive disorder Causes abnormal production of beta-globulin chains, due to a single amino acid substitution (glu6val) This results in the production of HbS rather than HbA Much more common in patients of African origin There are two genotypes: - HbSS – sickle cell anaemia phenotype - HbAS – sickle cell trait HbS polymerises when deoxygenated, causing RBCs to form “sickle cells” which are fragile and haemolyse, and can also block small vessels

Answer 54

HbAS confers protection from falciparum malaria rarely symptomatic => BUT vaso-occlusive events may occur in hypoxia – e.g. when flying or under anaesthesia

Answer 55

Usually on the newborn bloodspot screening Sickle cells can be seen on blood film Hb electrophoresis can confirm diagnosis and also distinguish variants.

Answer 56

Often presents in the first few months of life, with anaemia developing as HbF levels fall. Acute haemolytic crises occur, causing bone infarcts and painful dactylitis Untreated, there is: - Splenic infarction, leading to hyposplenism - Renal infarction, causing CKD - Cerebrovascular accidents In adulthood, there is normally a chronic haemolytic anaemia (60-90 g/L) but this is well tolerated unless there is a crisis.

Answer 57

Hyposplenism, CKD, Bone necrosis, Chronic leg ulcers, Iron overload (if multiple transfusions) Long-term pulmonary damage

Answer 58

Lifelong folate supplementation Pneumococcal vaccination and prophylactic penicillin (due to hyposplenism) Hydroxycarbamide (hydroxyurea) can help by increasing HbF production and is advised if there are frequent crises. Regular life-long transfusions (2-4 weekly), with iron chelators to prevent overload. Bone marrow transplantation is curative – but limited by availability of matched donors.

Answer 59

PAINFUL CRISES Occur due to micro-vascular occlusion, often affecting the bone marrow, causing severe pain. Can be precipitated by cold, infection, dehydration or hypoxia. Other presentations are mesenteric ischaemia (mimicking acute abdomen), cerebral infarctions or priapism

Answer 60

Due to parvovirus B19 Causes a sudden reduction in marrow production (particularly RBCs) Usually self-limiting, but transfusion may be required.

Answer 61

Mainly affects children as spleen has not yet undergone atrophy. Pooling of blood in the spleen +/- liver, with organomegaly, severe anaemia and shock Urgent transfusions are required.

Answer 62

Rarer Hb falls due to haemolysis

Answer 63

A-E resuscitation – high flow oxygen and IV fluids Strong analgesia within 30 minutes FBC, reticulocytes, XM blood Screen for signs of infection (culture, MSU, CXR) & treat early. Prophylactic enoxaparin should be given Fully cross-matched blood transfusion if Hb/reticulocytes fall sharply. Exchange transfusion if rapidly deteriorating.

Answer 64

Autoantibodies lead to extravascular haemolysis and spherocytosis Most commonly idiopathic, but can be secondary to lymphoproliferative diseases or other autoimmune diseases. Classified according to the optimal temperature at which antibodies bind to RBCs in vitro: 1. Warm AHA – IgG mediated; optimal binding 37 degrees => Treated with steroids or immunosuppresants +/- splenectomy 2. Cold AHA – IgM mediated; optimal binding below 4 degrees => Often associated with raynaud’s => Treated with cold-avoidance +/- chlorambucil

Answer 65

Penicillin-based drugs can cause formation of RBC antibodies Drugs such as quinine cause production of immune complexes

Answer 66

= Mechanical haemolysis caused by physical trauma in the circulation, due to: - Malignant HTN / pre-eclampsia - Haemolytic Uraemic syndrome - Thrombotic thrombocytopaenic purpura - Vasculitis (e.g. SLE) - DIC - Mechanical heart valves The blood film will show schistocytes irregular, asymmetrical cells).

Answer 67

Transplant/transfusion/rhesus reactions Immune-mediated, yet Coomb’s negative.

Answer 68

NEUTROPHILS – ingest and kill bacteria, fungi & cellular debris LYMPHOCYTES – produce antibodies for cell-mediated immunity. EOSINOPHILS – play a role in allergic reactions and defence against parasitic infection. MONOCYTES – precursor of tissue macrophages BASOPHILS – release histamine in inflammatory reactions

Answer 69

Bacterial infection Inflammatory reactions Disseminated malignancy Stress – e.g. surgery, burns Myeloproliferative conditions Corticosteroid therapy.

Answer 70

Viral infections Severe sepsis Neutrophil antibodies – e.g. SLE Bone marrow failure Hypersplenism – e.g. Felty’s Cytotoxic drugs

Answer 71

= A complete absence of circulating neutrophils Can be caused by drugs such as carbimazole/clozapine/etc.

Answer 72

Viral infections Chronic infections (TB, hepatitis) Myeloproliferative conditions

Answer 73

Bone marrow failure Corticosteroid therapy SLE Uraemia HIV Infection Cytotoxic drugs

Answer 74

Systemic activation of the coagulation pathways, leading to extensive intravascular coagulation and fibrin clot development. There is thrombotic occlusion of the arterial microvasculature The simultaneous depletion of clotting factors and consumption of platelets leads to haemorrhage. Eventually organ failure develops.

Answer 75

Infection Trauma Malignancy Obstetric complications (amniotic fluid emboli, pre-eclampsia) Severe liver failure Tissue destruction (pancreatitis/ burns) Toxic / immunogenic stimuli

Answer 76

Bruising Excessive bleeding from any sites Renal failure

Answer 77

Low platelets, low fibrinogen Raised PT & APTT Raised D-dimer Blood-film – broken RBCs (schistocytes)

Answer 78

Treat the cause Aggressive resuscitation, replacing platelets, coagulation factors (FFP) and fibrinogen (cryoprecipitate). Protein C – reduces mortality in multi-organ failure / severe sepsis.

Answer 79

The haematopoietic stem cell first divides into the common myeloid or lymphoid progenitor cell. COMMON MYELOID PROGENITOR cell then subdivides to form - Erythrocytes - Mast cell - Megakaryocytes (go on to form platelets) - Myeloblasts (go on to form monocytes, basophils, neutrophils, and eosinophils) COMMON LYMPHOID PROGENITOR cell subdivides to form: - NK cells - T and B lymphocytes

Answer 80

= Malignancy of lymphoid cells (of either B or T cell lineages), leading to uncontrolled proliferation of immature blast cells. Leads to eventual bone marrow failure and tissue infiltration Most common malignancy of childhood; it is rare in adults (“L for little”) More common in certain genetic syndromes – e.g. Down’s

Answer 81

Prognosis is good in children under 10 Poor prognosis suggested by: - older age of presentation, - male sex, - B-cell disease, - presence of Philadelphia chromosome (9:22 translocation).

Answer 82

= Malignancy of blast cells from the marrow myeloid elements. It can arise de novo, or on a background of myeloproliferative conditions/ previous chemotherapy/ ionising radiation/ genetic syndromes. Can occur at any age (median age of presentation = 65 years) – “M for mature”

Answer 83

Rapidly progressive => Only 20% 3-year survival after chemotherapy.

Answer 84

Regardless of subtype, acute leukaemias generally present with: B-symptoms => Fatigue, weight loss, night sweats, fevers, pruritis Bone pain from marrow infiltration Symptoms related to bone marrow failure => Anaemia (SoB on exertion, weakness) => Leucopaenia** (recurrent infections) => Thrombocytopaenia – bleeding/bruising (more common in AML) Hepatomegaly/ splenomegaly. ** Although presenting with leucocytosis, the cells are immature and non-functioning blast cells, thus symptoms of leucopaenia are seen.

Answer 85

FBC Blood film => Blasts are diagnostic => Lineage identified morphologically and confirmed with immunophenotyping CXR – T-cell ALL classically shows mediastinal widening Bone marrow aspiration – to confirm diagnosis and confirm lineage. PET scanning – to check for metastatic disease U&Es, LFTs and cardiac function testing (ECG/ echo) are essential for planning therapy.

Answer 86

Supportive care: - Barrier nursing - Hickman line for venous access - High-calorie diet - Frequent blood and platelet transfusions - Allopurinol to prevent tumour lysis syndrome due to chemotherapy. - Check frequent bloods and observations for sign of infection Antibiotics => If temperature is >38oC on 2 occasions greater than an hour apart, assume sepsis and start broad spectrum ABX until afebrile for 72 hours.

Answer 87

High-dose chemotherapy to induce remission => Then 2 years of maintenance therapy Consider marrow transplant if poor prognosis or relapse. Transplant is necessary to cure those with the Philadelphia chromosome

Answer 88

Intensive chemotherapy In disease with poor prognosis – allogenic marrow transplant from HLA-matched siblings is indicated after the first round of chemotherapy. => This then allows further high-dose chemotherapy In intermediate prognosis disease, autologous marrow transplants may be used (cells grown from own bone marrow) => Further chemotherapy must be at lower doses.

Answer 89

Rare in childhood, most common in people age 40-60 Philadelphia chromosome is present in 95% with CML Symptoms: - 30% are detected by chance - Insidious B symptoms are the most common presentation - Gout, due to purine breakdown - Abdominal discomfort due to splenic enlargement O/E: - Massive splenomegaly / hepatomegaly - Signs of anaemia/thrombocytopaenia.

Answer 90

FBC => WCC very high (raised across whole spectrum of myeloid cells) Blood film – spectrum of myeloid cells Bone marrow biopsy – hypercellular CT/PET Cytogenic analysis of blood/marrow for Philadelphia chromosome.

Answer 91

Imatinib chemotherapy is 1st line Stem cell transplant is the only treatment that may achieve remission, but carries significant mortality/morbidity.

Answer 92

Median survival 6 years. There are 3 phases: 1. Chronic phase – few symptoms, lasts for years 2. Accelerated phase – increasing symptoms, difficulty controlling counts 3. Blast transformation – features of acute leukaemia, eventual death.

Answer 93

= Most common leukaemia Median age at presentation = 70 years. Accumulation of mature B-cells that have escaped apoptosis, and this increasing mass of immune-incompetent cells leads to bone marrow failure. Presentation: - Often asymptomatic, found on routine FBC - May be anaemia or infection-prone - If severe, there can be B-symptoms O/E: - Enlarged non-tender lymph nodes - Hepatosplenomegaly

Answer 94

FBC - Markedly raised lymphocytes - May be signs of bone marrow failure - Autoimmune haemolysis develops later Blood film – predominant SMUDGE cells (small mature lymphocytes).

Answer 95

Without treatment: - 1/3rd never progress - 1/3rd will eventually progress - 1/3rd actively progress from diagnosis. Treatment is thus only indicated if symptomatic, or there are cytogenic markers of poor prognosis. Treatment can be with chemotherapy or radiotherapy.

Answer 96

prognosis depends on Rai stage (stage 0 - 4) Death is usually due to infection, or transformation to an aggressive lymphoma (Richter’s syndrome).

Answer 97

= catecholamine secreting tumours, arising from sympathetic paraganglionic cells (known as chromaffin cells).

Answer 98

usually located in adrenal medulla 10% are extra-adrenal 10% are bilateral 10% are familial => MEN 2a/2b => Neurofibromatosis => Von Hippel-Lindau Syndrome

Answer 99

Usually severe/episodic HTN, unresponsive to medical treatment. Also often vague episodic symptoms: - General – sweating, heat intolerance, pallor or flushing - Neurological – headaches, visual disturbances, seizures - CV – palpitations, chest tightness, dyspnoea, postural hypertension - GI – abdominal pain, nausea, constipation Symptoms may be worsened by stress, exercise or drugs.

Answer 100

3x 24-hour urine collections for raised free metadrenaline and nor-metadrenaline. MRI/CT/functional imaging to locate the tumour

Answer 101

Alpha blockade with phenoxybenzamine. Beta-blockers AFTER alpha blockade is established => Used if significant tachycardia remains after alpha blockade. Surgical excision

Answer 102

Should only be initiated after alpha-blockade. => can induce life-threatening hypertensive episodes in patients without adequate alpha blockade.

Answer 103

= Primary Adrenal Insufficiency Destruction of the entire adrenal cortex, leading to deficiencies in: 1. Glucocorticoid (cortisol) 2. Mineralocorticoid (aldosterone) 3. Sex steroids

Answer 104

HPA disease generally spares mineralocorticoid production, which is stimulated by ATII.

Answer 105

- Autoimmune (most common in UK) - TB (most common worldwide) - Overwhelming sepsis - Metastatic cancer – lung/breast - Lymphoma - Adrenal Haemorrhage (Waterhouse-Friedrichsen syndrome)

Answer 106

Symptoms: - Often vague and non-specific - Weight loss, malaise, weakness, myalgia - Syncope - Depression Signs: - Pigmentation, especially of new scars and palmar creases. - Postural hypotension - Signs of dehydration - Loss of body hair (particularly axillary/pubic)

Answer 107

Bloods: - U&Es – low sodium, high potassium (due to mineralocorticoid insufficiency). - Calcium – raised - Glucose – low, due to lack of cortisol Short ACTH stimulation test / Synacthen Test - Measure plasma cortisol before, and 30 mins after. - A 2nd value >550nmol/L excludes Addison’s 9am ACTH/cortisol => Raised ACTH and low/normal cortisol confirms Addison’s Investigations for cause: - 21-hydroxylase adrenal autoantibodies – autoimmune - CXR – TB - Adrenal CT – to look for TB/metastatic disease

Answer 108

- Give tetracosactide IM (ACTH analogue). - Measure plasma cortisol before, and 30 mins after. - A 2nd value >550nmol/L excludes Addison’s

Answer 109

Long-term glucocorticoid cover: => 15-25mg HYDROCORTISONE daily, in 3 divided doses (mimic diurnal variation) => Avoid giving late in the day, as can cause insomnia. Long-term mineralocorticoid cover: => Required if postural hypotension => FLUDROCORTISONE 50-200 micrograms daily. Patient education: - Steroids should never be abruptly stopped - Extra doses of steroid are needed for strenuous exercise, surgery, febrile illness, or trauma. - Patient should have a steroid card/bracelet and should carry IM hydrocortisone in case of Addisonian Crisis.

Answer 110

Severely inadequate levels of cortisol, occurring either as a first presentation of adrenal disease or triggered by physiological stress. Presents with: - Fever, N&V - Shock - Hypoglycaemia - Hyponatraemia and hyperkalaemia Treat with IV fluids and IV hydrocortisone as part of resuscitation.

Answer 111

Due to congenital deficiency in 21-alpha-hydroxylase => This enzyme is necessary for the production of mineralocorticoids and glucocorticoids (but not sex hormones) Autosomal recessive. Aldosterone and cortisol levels decrease, and thus ACTH rises. => Precursors such as progesterone build-up and go down the alternative pathway to form sex hormones => testosterone levels raised

Answer 112

Virilisation of the external genitalia in females => Clitoral hypertrophy (resembling a penis) and variable fusion of the labia (resembling a scrotum). Enlarged penis and pigmented scrotum is seen in males (but rarely noticed). Presents with salt-losing crisis in 80% of males at 1-3 weeks of age (failure to thrive, and potentially fatal hypovolemia and shock) In the non-salt-losing males, presents as hyper-virilisation (early pubarche, adult body odour, muscular build).

Answer 113

17-alpha-hydroxyprogesterone levels = markedly raised => this is diagnostic Other features may be: - Low sodium - High potassium - Metabolic acidosis

Answer 114

Steroid cover, as per Addison’s disease. Also at risk of Addisonian crisis.

Answer 115

Adrenal adenoma, leading to primary hyperaldosteronism Most common in young females. Hyperaldosteronism leads to sodium and water retention.

Answer 116

Mostly asymptomatic HTN (resistant to Tx) Features of hypokalaemia (Cramps, weakness, tetany, polyuria)

Answer 117

Biochemical features: => Hypernatraemia, Hypokalaemia => Elevated plasma aldosterone:renin ratio => Plasma aldosterone levels will not be suppressed by fludrocortisone administration. Further Investigations: => Once primary hyperaldosteronism is confirmed, adrenal CT is indicated => Adrenal scintography is alternative method (Unilateral uptake of the isotope in Conn’s)

Answer 118

Laparoscopic adrenalectomy to remove adenoma Spironolactone pre-op to control HTN/hypokalaemia.

Answer 119

= anything causing blood stasis or hypercoagulability - Age/immobility - Pregnancy/OCP - Malignancy - Obesity - Surgery (typically occur 2 weeks post-surgery) - Previous DVT

Answer 120

Most DVTs are silent Classical Clinical features: - Calf tenderness & firmness - Oedema - Erythema & calor - Distension of superficial veins - Superficial thrombophlebitis Atypical Presentation: - Ilio-femoral thrombosis can present with severe pain, but few physical signs. - Complete occlusion of a large vein can lead to cyanotic discolouration.

Answer 121

Calculate Well’s Score – by risk stratifying to low risk (Wells’ Score <2) and a negative d-dimer the clinician can exclude the need for ultrasound (US) to rule out DVT. D-dimer = Highly sensitive, not specific for DVT (also increased in infection, pregnancy, malignancy, post-op etc.) => If pre-test probability is low and D-dimer is negative – can r/o DVT => If D-Dimer is positive or high/intermediate pre-test probability, do compression USS. Compression USS: => Non-collapsing veins indicate presence of DVTs Thrombophilia screen => Ensure this is done prior to commencing anticoagulant therapy if there are no pre-disposing factors.

Answer 122

Stop COCP 4 weeks pre-op Mobilise as early as possible Immobile patients should be heparinised At risk patients should have TEDs/intermittent pneumatic pressure until 16 hours post-op.

Answer 123

LMWH to prevent propagation of the clot Warfarin started simultaneously => LMWH can be stopped when INR = 2-3 Length of warfarin treatment: - 3 months for post-op DVT - 6 months if there was no precipitating cause - Lifelong if known thrombophilia/recurrent DVT

Answer 124

Classically present with: - Sudden-onset breathlessness - Pleuritic pain - Haemoptysis However, PE should be included in almost any respiratory differential as they are so common and variable in presentation. Possible Signs: - Evidence of a DVT - Raised JVP - Cyanosis if embolus is large

Answer 125

~5% of PEs >60% of the pulmonary circulation is blocked Leads to rapid cardiovascular collapse

Answer 126

~10% of PEs Middle-sized pulmonary arteries are blocked Leads to breathlessness, pleuritic chest pain and haemoptysis

Answer 127

~85% of PEs Small peripheral vessels are blocked Patients may be asymptomatic or classical presentation. Massive PE may ensue following minor PE (known as premonitory embolus)

Answer 128

FBC, U&E, clotting, D-dimer ABG – T1RF CXR => Often normal -> May see dilated pulmonary artery or wedge-shaped opacities ECG: => Tachycardia, RBBB, RV strain => Classical SIQIIITIII is rare Echo: => Can confirm right heart strain CTPA = gold-standard => V/Q if this is unavailable, but less accurate

Answer 129

Large S wave in lead I Q-wave in lead III T wave inversion in lead III Rare; but sometimes seen in PE (sign of right-heart strain)

Answer 130

Major/minor PE should be managed as per DVT. Massive PE: - Emergency A-E resuscitation - IV morphine + antiemetic - Heparin therapy – LMWH/UH If SBP >90mmHg – commence anticoagulant therapy If SBP <90mmHg – start vasopressors (noradrenaline) before commencing thrombolytic therapy.

Answer 131

* Diabetes mellitus (20-40%) * HTN * Chronic glomerulonephritis * Chronic pyelonephritis * Obstructive uropathy * Renovascular disease * Drugs (e.g. long-term NSAIDs) * PKD

Answer 132

Often asymptomatic until very advanced – may be some vague fatigue and anorexia. - Polyuria/nocturia - Restless leg syndrome - Sexual dysfunction - Nausea & Pruritis (early uraemia) - Yellow pigmentation, encephalopathy and pericarditis (severe uraemia) - Pedal oedema & pulmonary oedema.

Answer 133

- Pallor – due to anaemia - Excoriations – due to pruritis - Hypertension/fluid overload signs - Pericardial rub (rare) - Proteinuria

Answer 134

diagnosed when any two tests, 3 months apart show reduced eGFR and can be stages 1-5 depending on the level of reduction. (in some situations a 24-hour urinary creatinine may be collected to calculate true creatinine clearance)

Answer 135

eGFR >90 Normal eGFR but urine findings/structural abnormalities/ genetic traits suggest CKD. Asymptomatic

Answer 136

GFR 60-89 Mildly reduced eGFR and other findings (as for stage 1) point to CKD Asymptomatic

Answer 137

eGFR 45-59 = Moderate CKD Usually asymptomatic

Answer 138

eGFR 30-44 = Moderate – severe CKD Pts are often anaemic

Answer 139

eGFR 15-29 = Severe CKD Symptoms often at eGFR <20 Electrolyte disturbances

Answer 140

eGFR <15 / dialysis = End-stage renal failure (ESRF) Significant complications and symptoms Dialysis usually at eGFR <10

Answer 141

Bloods: => FBC, U&Es, LFTs, calcium, phosphate, PTH levels, Glucose Urinalysis: - Any blood? - Quantify proteinuria - Exclude infection - May do 24-hour urinary protein / creatinine clearance - To assess severity / for nephrotic syndrome CXR – ?pulmonary oedema. ECG – if hyperkalaemia Renal USS: - To exclude obstruction - Can look for polycystic kidneys Further Ix: - Renal biopsy – if cause unclear - Renal DTPA scan – investigate vascular supply - Bone imaging – screen for renal bone disease

Answer 142

Treat reversible causes – e.g. obstruction, nephrotoxic drugs 1st line = BP control/diabetic control => BP controlled to <130/80 => If proteinuric, BP <125/75 (ACEi 1st line) Primary CV prevention is also important (statin and low-dose aspirin) 2nd line = control of complications => Recombinant EPO for anaemia => Calcium/vitamin D supplementation for bone disease => K+ restriction for hyperkalaemia Renal replacement therapy is indicated in those with ESRD = dialysis or transplantation => Any symptomatic CKD stage 5 patient

Answer 143

Renal Anaemia Renal Bone disease Secondary HTN Electrolyte disturbances Myopathy Peripheral neuropathy Increased risk of infection GI – Anorexia, N&V Pericarditis Depression is common – particularly in later stages/dialysis

Answer 144

In CKD, the kidney partly loses its secretory EPO function, leading to anaemia. => Correlates with the severity of renal disease Recombinant EPO can be given to those on dialysis with ESRD as part of renal replacement therapy to combat this anaemia Target Hb 100-120

Answer 145

In CKD the kidneys produce less 1-alpha-hydroxylase and excrete less phosphate => low VitD, low Calcium, hyperparathyroidism => Ultimately osteopaenia and osteoporosis Tx: - Restriction of dietary phosphate, - Phosphate binders (calcichew) - AdCal (calcium and vitD supplementation).

Answer 146

ESRF is not a clear cut line, and RRT may be required at different levels in different individuals, but general indications are: A intractable acidosis E electrolyte disturbance (hyperkalaemia, hyponatraemia, hypercalcaemia) I Intoxicants O intractable fluid overload U uraemia symptoms

Answer 147

Diffusion of solutes between blood and dialysate, which flow in opposite directions with a semi-permeable membrane between. Vascular access is most commonly achieved by: 1. AVF (at the wrist / cubital fossa) 2. Double lumen arterial lines (vascath / permcath) Dialysis must occur for 4 hours, three times weekly. - Normally occurs at hospital - Home treatment is available, but requires support and training in dialysis unit. The main issue is haemodynamic instability during dialysis

Answer 148

Continuous ambulatory peritoneal dialysis patients instil up to 2 litres of isotonic/ hypertonic solution into the peritoneal cavity. This then equilibrates with the blood in peritoneal capillaries. The fluid is then drained out after 2 hours. This is performed 3-4 times daily at home Main risk is peritonitis

Answer 149

There is no difference in clinical outcomes between peritoneal and haemodialysis.

Answer 150

Patient assessment: - Virology / TB status – active infection is a CI due to risks of immunosuppression - Blood group / HLA matching - Full systemic examination – comorbid disease is a CI. Prognosis is good => 1 year graft survival rate of 90-95% depending on extent of HLA match

Answer 151

Operative – bleed, thrombosis, infection, urinary leaks. Rejection – risk highest in 1st 3 months; need lifelong immunosuppression Ciclosporin / Tacrolimus toxicity Infection / malignancy due to immunosuppression (typically skin cancer, anal cancer, lymphoma).

Answer 152

Lie in the retroperitoneum of the abdomen. Typically extend from T12 to L3. => The right kidney is generally lower than the left due to the liver. The kidney parenchyma consists of two main regions, covered with a fibrous capsule: 1. inner medulla 2. outer cortex

Answer 153

RENAL CORPUSCLE - site of initial filtration PCT - reabsorption of ions and solutes; regulation of pH by secreting bicarbonate LOOP OF HENLE - Ascending limb aims to create a strong osmotic gradient for absorption of large amounts of water from the descending limb DCT - Secretion of ions, acids, drugs and toxins; Variable reabsorption of water/sodium under the control of aldosterone. COLLECTING DUCT - Variable reabsorption of water under the control of ADH

Answer 154

The juxtaglomerular cells of the kidneys are stretch receptors: 1. Decrease in blood volume => reduced stretch 2. Leads to the release of renin. 3. Renin is involved in the cleavage of angiotensinogen to form AI 4. AI undergoes conversion by ACE to form AII Angiotensin II causes: - Vasoconstriction (of afferent arteriole) => BP increases until it returns to normal - Release of aldosterone from the adrenal cortex => Enhances reabsorption of sodium and water (and increases secretion of K+ and H+), thereby increasing blood volume.

Answer 155

Pseudo-hyperkalaemia (Haemolysis, Incorrect order of blood draw, Sample taken from drip arm) AKI / CKD Drugs: => Supplements, K+-sparing diuretics, ACEis, NSAIDs Acidosis (including DKA) Addison’s disease Tumour-lysis syndrome Burns

Answer 156

Often asymptomatic if mild/moderate Muscle weakness, numbness, tingling, N&V Palpitations (=> arrythmias if untreated)

Answer 157

Raised K+ on U&Es / blood gas ECG signs: - Tall, peaked T waves - Widened QRS complexes - Flattened P-waves / prolonged P-R interval If it goes untreated, ventricular fibrillation / tachycardia can develop.

Answer 158

Aims of Tx: 1. Stabilise the Heart – Calcium Gluconate 2. Drive potassium intracellularly – insulin & dextrose / salbutamol 3. Tackle the underlying issue to reduce total body potassium

Answer 159

If potassium >6.5 mmol/L or there are ECG changes, initiate emergency management: 1. Start continuous ECG monitoring 2. 10ml of 10% Calcium gluconate IV to stabilise the heart => Repeat at 5 min intervals until a max of 3 doses or ECG normal 3. 50ml 50% glucose with 10 units Actrapid Insulin into a large vein over 30 minutes to decrease K+ concentration => Onset 1-4 hours, consider BM 4. Consider 10mg Salbutamol neb 5. If pH <7.2, consider sodium bicarbonate IV (if advised by renal registrar) 6. Recheck K+ after 2 hours 7. Consider potassium binders 8. Ensure the underlying cause is being treated.

Answer 160

= a sudden deterioration in kidney function occurring over hours or days, as measured by serum urea and creatinine. This results in a failure to maintain fluid, electrolyte and acid-base homeostasis. Can be PRE-RENAL, RENAL or POST-RENAL

Answer 161

Occurs when renal perfusion is interrupted Main causes: 1. Shock – hypovolaemic, cardiogenic, distributive. 2. Renovascular obstruction: - AAA, - Renal artery stenosis (and ACEis given in bilateral renal artery stenosis), - Renal vein thrombosis If interruption in the blood supply is prolonged, there will be acute tubular necrosis (ATN)

Answer 162

Occurs when there is obstruction of the urinary tract Blockage is often in the ureters – e.g. stones, strictures, clots, external/internal malignancy. Can also be due to bladder outlet obstruction – e.g. prostatic enlargement, urethral strictures, paraphimosis.

Answer 163

If there is no pre-renal or post-renal cause of AKI, then intrinsic cause should be suspected Injury or damage to the renal parenchyma, by 3 mechanisms: 1. Acute Tubular Injury (85%) 2. Interstitial Nephritis (10%) 3. Glomerular Disease (5%)

Answer 164

Renal causes are due to drugs/toxins damaging the tubular cells (rather than ischaemia, which is pre-renal). Drugs – aminoglycosides, cephalosporins, radiological contrast mediums, NSAIDs. Toxins – heavy metal poisoning, myoglobinuria, haemolytic uraemic syndrome (HUS).

Answer 165

Follows an episode of rhabdomyolysis (muscle breakdown from trauma, strenuous exercise or medications), releasing myoglobin which is readily filtered by the glomerulus. Gives the classical dark urine, but in high quantities will precipitate out within the tubules to cause damage. Causes ACUTE TUBULAR INJURY & thus AKI

Answer 166

Occurs in children following diarrhoeal illness caused by verotoxin-producing E. coli O157, or following a URTI in adults. Thrombocytopaenia, haemolysis and ACUTE TUBULAR INJURY (=> AKI). Children recover within a few weeks, prognosis for adults is poor. Treatment is supportive, including dialysis.

Answer 167

Damage is not limited to tubular cells (as in ATN) and bypasses the basement membrane to cause damage to the interstitium. Most commonly caused by drugs (especially antibiotics, but also diuretics, NSAIDs allopurinol and PPIs). Can be caused by infection, auto-immune mechanism or lymphoma. Normally responds to withdrawal of the drugs and a short course of oral steroids.

Answer 168

Glomerulonephritis, thrombosis, HUS, IgA nephropathy

Answer 169

Symptoms: - Reduced urine output - Nausea and vomiting - Dehydration - Confusion - Fatigue Signs - Dependent on the underlying cause – look for: - Fluid overload - Hypotension in pre-renal causes, HTN in CKD - Palpable abdominal mass - Associated features of vasculitis – petechiae, skin changes, bruising, etc.

Answer 170

1. Is it AKI or CKD? => Suspect CKD if history of comorbidities (HTN, DM) and long duration of Sx (confirm with USS showing small kidneys) 2. If it is AKI, is it pre-renal / renal / post-renal? => Pre-renal – look for signs of shock and treat appropriately; listen for renal bruits and take vascular Hx => Post-renal – order abdominal or KUB USS; examine prostate in older males. => Renal – drug history, Hx of recent infections / joint pains/ rashes; urine dip (?blood / protein); any red cell casts on microscopy

Answer 171

NICE recommends using any of the following criteria: 1. A rise of serum creatinine >26 micromol/L in 48 hours 2. A 50% or greater rise in serum creatinine over the past 7 days 3. A fall in urine output to <0.5mL/kg/hour for > 6 hours

Answer 172

SERUM CREATININE 150-200% increase OR >25 micromol/L increase in 48h URINE OUTPUT <0.5 mL/kg/hour for 6h

Answer 173

SERUM CREATININE 200-300% increase URINE OUTPUT <0.5 mL/kg/hour for 12h

Answer 174

SERUM CREATININE >300% increase OR >350 micromol/L increase in 48h URINE OUTPUT <0.3 mL/kg/h for 24h OR Anuria for 12h

Answer 175

In order to confirm oliguria/anuria, the patient first needs to be volume replaced to ensure they are euvolaemic.

Answer 176

BEDSIDE Urine dip and MC&S Observations Glucose ECG – ?hyperkalaemia BLOODS FBC, U&E, LFTs, clotting, CRP ABG/VBG – ?acid-base imbalance Nephritic Screen if cause unclear Creatine Kinase (if indicated) IMAGING Renal USS to rule out obstruction CXR if pulmonary oedema CT KUB if obstruction

Answer 177

ANCA & anti-GBM – Rapidly progressive glomerulonephritis (RPGN) ANA, dsDNA & complement – SLE Immunoglobulins, serum electrophoresis – myeloma Rheumatoid Factor – RA-associated GN Hepatitis B/C screen – Mesangiocapillary glomerulonephritis (MCGN) ASO – post-streptococcal

Answer 178

A – E assessment (with correction of any hypoxia) Hold any potentially damaging drugs Restrict potassium intake Then manage cause: PRE-RENAL = Treat shock RENAL = Assess fluid status Volume replacement (normal saline) to match losses (fluid balance chart) If there is urine output after fluid replacement, continue large quantities of fluid +/- diuretics – furosemide stress test If there is no urine output / there are complications – nephrologist input POST-RENAL = Refer to urology

Answer 179

Hyperkalaemia Hypernatraemia (unless pre-renal cause) Metabolic acidosis Rapidly progressive Uraemia Volume overload => pulmonary oedema CKD and End-stage renal disease

Answer 180

= swelling which results from an increased quantity of fluid in the interstitial space of soft tissues, due to failure of lymphatic drainage. Can be PRIMARY or SECONDARY It causes chronic, non-pitting oedema – commonly affecting the legs and progressing with age

Answer 181

Presents in early life Due to an inherited deficiency of lymphatic vessels (e.g. Milroy’s disease)

Answer 182

Due to obstruction of lymphatic vessels (e.g. filarial infection, repeated cellulitis, malignancy, post-op).

Answer 183

Lymphoscintography can be used to confirm diagnosis, after other causes of oedema have been excluded (CCF, renal disease, deep venous insufficiency).

Answer 184

Elevation Compression stockings Physical massage Long-term ABX if recurrent cellulitis (each episode further damages lymphatic drainage).

Answer 185

Phenomenon = general term describing episodic digital vasospasm in the absence of an identifiable associated disorder. Syndrome = Raynaud’s phenomenon occurring secondary to another condition

Answer 186

Connective Tissue Disease : - Systemic Sclerosis - Mixed connective tissue disease - SLE - Sjogren’s syndrome - Polyarteritis Nodosa Macrovascular Disease: - Atherosclerosis - Thoracic Outlet Obstruction - Buerger’s disease Occupational Trauma - Vibration white finger - Repeated extreme cold or chemical exposure Drugs - Beta-blockers - Cytotoxic drugs Others - Malignancy - AVF

Answer 187

Common triggers = cold exposure or emotional stress. There are 3 phases: 1. Pallor – due to digital artery spasm 2. Cyanosis – due to accumulation of deoxygenated blood 3. Rubor – erythema due to reactive hyperaemia. As the fingers return to normal, there may be numbness or a burning sensation and severe pain. Attacks are usually <45 minutes; but can last for hours. => Very severe cases can involve tissue infarction and loss of digits.

Answer 188

Primary Raynaud’s does not require further investigation. if any features suggesting secondary cause: - FBC, U&E, coagulation, glucose - TFTs - ANA/RF/APA – autoimmune screen if suspecting secondary cause.

Answer 189

Keep extremities warm Smoking cessation Stop exacerbating drugs – e.g. beta-blockers, OCP 1st line medical therapy = nifedipine => Losartan/prazosin/fluoxetine = 2nd line Sympathectomy may help those with severe disease, but may be short lived.

Answer 190

Paracetamol = intrinsic hepatotoxin - It is conjugated with glucuronide and sulphate at therapeutic doses. - A small amount is metabolised by mixed function oxidase systems to form NAPQI - NAPQI is immediately conjugated with glutathione due to its toxicity. - In overdose, the normal conjugation pathways become saturated - Large amounts of NAPQI are created. - This overwhelms the liver glutathione stores to cause cellular damage. Severity is dose-related, however those who are malnourished/low weight or with high alcohol intake appear to be more susceptible.

Answer 191

Most remain asymptomatic for 24 hours – or at most develop anorexia, nausea and vomiting. Symptoms/signs start to develop after 24 hours: - RUQ pain - Metabolic acidosis - Hypotension - Hypoglycaemia - Pancreatitis - Arrythmias Liver damage is not detectable on blood tests until 18 hours after ingestion. => Damage peaks at 72-96 hours post-ingestion (deranged ALT/ALP and INR) Without Tx, some develop fulminant liver failure. Renal failure due to acute tubular necrosis can also occur.

Answer 192

A-E approach Lavage if >12g (>150mg/kg) taken within 1 hour. Give activated charcoal if <1 hour since ingestion. Take a full set of bloods at 4 hours post ingestion - Including INR, ABG, LFTs, U&Es, glucose, blood salicylate and paracetamol level If <8 hours after ingestion – give IV acetylcysteine if blood levels above the treatment line on the hospital protocol. If >8 hours after ingestion – treat immediately with N-acetylcysteine if >150mg/kg has been ingested. => Discontinue if plasma levels return below the treatment line, and the patient is asymptomatic with normal biochemistry. If the patient continues to deteriorate then discuss with the liver team. Discharge only after mental health team review.

Answer 193

Paracetamol level is unreliable before the 4-hour mark due to continuing absorption/distribution

Answer 194

Replenishes cellular glutathione stores and may repair oxidative damage. Potential SEs: - Rash, oedema, hypotension, bronchospasm (rarely serious; treated with IV chlorphenamine). - Only stop the infusion in true anaphylaxis

Answer 195

Infection => E.g. IE, bacterial sepsis, EBV, TB, malaria, schistosomiasis. Inflammation => E.g. RA, SLE, sarcoidosis Portal HTN Haematological disease => Haemolytic anaemia, leukaemia, lymphoma, myeloproliferative disorders -- MASSIVE splenomegaly (palpable in the RIF) can be seen in myelofibrosis, CML, lymphoma, malaria, leishmaniasis or Gaucher’s disease.

Answer 196

Splenomegaly of any cause can lead to hypersplenism, which results in: 1. Pancytopaenia 2. Increased plasma volume 3. Haemolysis

Answer 197

= largest lymphoid organ in the body functions to break down erythrocytes and for immunological defence

Answer 198

Most commonly caused by blunt trauma, occasionally by penetrating injuries. Pre-existing illness can markedly increase the risks of splenic injury Presentation: - Immediate massive bleeding - Peritonism from progressive blood loss - Eventually shock Rupture can occur hours-days after the initial trauma, due to expanding haematoma beneath the capsule (asymptomatic interval).

Answer 199

1. Ascending spread from cholangitis 2. Portal spread from a focus of sepsis in the abdomen 3. Systemic bloodstream spread in septicaemia

Answer 200

Most common organisms: - E. coli - Strep. Milleri - Anaerobes Presentation: - Patients are often not acutely unwell, may just have a long history of malaise. - Can present acutely unwell with abdominal sepsis and a tender enlarged liver. - May be pleural effusion in the right lower chest.

Answer 201

USS/CT can detect a liver abscess. CXR may show elevation of the right hemidiaphragm +/- pleural effusion

Answer 202

Aspiration under USS guidance. IV ABX Treat underlying cause

Answer 203

Consider in patients with a Hx of travel. Faeco-oral spread of entamoeba histolytica. Presentation: - May be asymptomatic - Can get profuse/bloody diarrhoea - Swinging high fever, RUQ pain and tenderness

Answer 204

Stool microscopy will show offending organism, blood and pus. USS/CT to visualise the abscess

Answer 205

Metronidazole for 5 days = Tx for amoebic dysentery USS drainage may also be required.

Answer 206

Caused by echinococcus granulosis (dog tapeworm). Infects humans coming into contact with infected dogs or food/water contaminated with dog faeces. Thick-walled, slow-growing cyst Either Asymptomatic or dull ache in RUQ

Answer 207

Positive hyatid complement fixation test/haemagglutination, eosiniphilia. AXR – may show calcification of cyst wall USS/CT – shows cyst

Answer 208

Albendazole and FNA under USS guidance Deworming of pet dogs.

Answer 209

90% of liver tumours are secondary metastases. Primaries commonly in the lung/stomach/colon/breast/uterus. Management = investigation to find the primary

Answer 210

= Malignant tumour of hepatocytes – accounts for the majority of primary liver cancers. Common in China and Sub-Saharan Africa (rare in the west) Causes: - Chronic hepatitis / cirrhosis - Metabolic liver diseases - Aspergillus aflatoxin - Parasites - Anabolic steroids

Answer 211

Symptoms: - Non-specific fever, malaise, weight loss. - RUQ pain Signs: - Hepatomegaly (may be smooth or hard/irregular) - Signs of chronic liver disease / decompensation - Abdominal mass / bruit over liver - Jaundice is late presentation

Answer 212

Bloods – FBC, LFTs, clotting, hepatitis serology, AFP (raised in >50% of HCC) USS/CT to identify lesions and guide biopsy MRI to distinguish between benign/malignant lesions ERCP/biopsy if cholangiocarcinoma suspected

Answer 213

Surgery for solitary HCCs <3cm, but high risk of recurrence Liver transplantation if there are small tumours due to cirrhosis => Resection in cirrhosis can lead to decompensation

Answer 214

Most commonly haemangiomas (incidental finding on CT/USS) If the patient is a young woman on the OCP, it may be more likely to be a liver cell adenoma. A benign liver tumour should only be treated if large/symptomatic

Answer 215

= yellow discolouration of the sclera, skin and mucous membranes secondary to hyperbilirubinaemia Generally, the bilirubin needs to be around 2x the upper limit to be clinically visible

Answer 216

1. Bilirubin is a product of haemoglobin breakdown. When a red cell is broken down (typically in the spleen), this releases unconjugated bilirubin (UCB). 2. UCB is binds to albumin before being transported to the hepatocytes of the liver. 3. In the liver it is conjugated by a hepatic enzyme. This conjugated bilirubin (CB) is then stored in the gallbladder as part of bile. 4. Bile is released during digestion, where the CB is then broken down in the small intestine into Urobilinogen. 5. Urobilinogen then takes 1 of 3 paths: - Converted to stercobilin in the gut and excreted in the stool - Absorbed into blood before being excreted by the kidney in the urine. - Recycled back to the liver to be re-excreted in bile.

Answer 217

Stercobilin gives stools their dark colour Urobilinogen in the urine is oxidised to urobilin when exposed to air, eventually giving the urine a dark colour (as opposed to immediate dark urine of cholestasis, which is caused by conjugated bilirubin).

Answer 218

1. Pre-hepatic – Increased RBC breakdown 2. Hepatic – Dysfunction of hepatocytes 3. Post-hepatic – Cholestasis due to obstruction

Answer 219

Occurs due to increased breakdown of RBCs leads to increased UCB – this overwhelms the capacity of the hepatocytes to conjugate it There will be leftover UCB in the bloodstream and results in jaundice. Causes = anything causing haemolysis.

Answer 220

Hepatitis (Viral, autoimmune, alcoholic) Cirrhosis Drug-induced liver injury Wilson’s Disease Jaundice occurs due to: 1. UCB not conjugated at a sufficient rate, leading to increased circulating UCB. 2. A degree of obstruction means that CB not being transported into biliary ducts, CB builds up in the hepatocytes and ends up in the bloodstream (increased circulating CB).

Answer 221

= hyperbilirubinaemia with no other blood test abnormalities (i.e. LFTs and reticulocytes) DUE TO GILBERT'S SYNDROME

Answer 222

Autosomal recessive inherited condition Leads to defective gene encoding for the hepatic conjugation enzyme. Intermittent jaundice in the absence of haemolysis or underlying liver disease. Will see isolated elevated UCB on investigation => Normal LFTs and reticulocytes Benign and self-limiting condition

Answer 223

Urinary urobilinogen may be raised (due to inability of the liver to re-excrete what is reabsorbed) If conjugated bilirubin levels are high enough => dark urine. Stools could be paler than usual (due to a decrease in the ability to conjugate bilirubin and excrete it into the gut)

Answer 224

Large amounts of bilirubin excreted into the gut => normal stools Urinary urobilinogen also raised (but no clinically dark urine as takes time to oxidise). UCB cannot be excreted in urine

Answer 225

Due to obstruction of bile outflow from the liver – leading to cholestasis. Obstruction can be INTRA or EXTRA-HEPATIC => Pressure backs up bile between hepatocytes back to vasculature and CB is pushed back into the bloodstream (conjugated hyperbilirubinaemia).

Answer 226

Hepatitis Cirrhosis Neoplasm Drugs (chlorpromazine, flucloxacillin, isoniazid, OCP) Pregnancy

Answer 227

Gallstones Cholangiocarcinoma Primary sclerosing cholangitis Congenital atresia of CBD Pancreatitis Tumour of pancreatic head

Answer 228

Pale stools – very little/no bilirubin reaching the GI tract. Dark urine – conjugated bilirubin reaches the kidneys through the blood.

Answer 229

Bloods: => FBC, reticulocytes, LFTs, U&Es, clotting, glucose, bilirubin levels. Urinary urobilinogen/bilirubin Further Investigations: - Blood films / Coomb’s test – if ?haemolysis - Viral serology/autoantibodies – if ?hepatitis - USS - ?dilated duct system - CT/MRI - intrahepatic / pancreatic lesions ERCP if ductal system dilated on USS

Answer 230

Viral infections (Hep A-E or non-Hep infections) Autoimmune Drug reactions Alcohol

Answer 231

Hepatitis B +/- D virus Hepatitis C virus Autoimmune hepatitis Alcohol Hyperlipidaemia (NAFLD) Drugs (methyldopa, nitrofurantoin) Metabolic disorders (Wilson’s, alpha1-antitrypsin deficiency, haemochromatosis)

Answer 232

Done in any patient with suspected hepatitis / liver pathology of unknown origin Microbiology – viral screen Clinical chemistry: - Ferritin / transferrin - Lipids - Caeruloplasmin - AFP - Alpha-1 antitrypsin Immunology – autoantibodies Abdominal USS

Answer 233

Transmitted faeco-orally Notifiable disease Does not lead to chronic liver disease, thus there are no carriers. No specific treatment

Answer 234

Transmitted faeco-orally Clinically similar to HepA infection: - Causing epidemics of acute, self-limiting hepatitis - No progression to chronic disease Common in indo-china, so consider if recent travel. Can cause severe disease in pregnant women

Answer 235

transmitted in blood/semen/saliva via skin breaks or mucous membranes Vertical transmission = common worldwide Around 10% of those infected will develop chronic disease 1% will develop fulminant liver disease

Answer 236

Unprotected sex with multiple partners / someone who is infected Sharing needles MSM Living with someone with chronic HBV Infant born to infected mother Job that exposes you to human blood Travel to regions with high infection rates of HBV, such as Asia, the Pacific Islands, Africa and Eastern Europe

Answer 237

= Incomplete RNA virus Can only cause infection in the presence of Hep B (as it requires the HepB virus for its own assembly). Also transmitted by bodily fluids Can be both acute and chronic It can be acquired simultaneously with Hep B, or occur later. Patients with Hep D superadded to HepB infection are more likely to develop fulminant liver disease.

Answer 238

clinically similar to HepB infection Transmitted via bodily fluids Particularly common in IVDUs Vertical transmission is rare, and sexual transmission is uncommon About 85% become chronically infected 30% get cirrhosis in 20 years.

Answer 239

Pathological changes are the same, regardless of cause. Hepatocytes undergo degenerative changes (swelling & vacuolation) before necrosis and rapid removal. Extent can vary from scattered necrosis to multiacinar necrosis leading to fulminant hepatic failure.

Answer 240

= Defined as any hepatitis lasting more than 6 months. Chronic inflammatory cell infiltrates are present in the portal tracts. There may be loss of definition, necrosis and fibrosis. This eventually leads to cirrhosis The overall severity is judged by the degree of inflammation (grading) and the extend of fibrosis/cirrhosis (staging). => Using various scoring systems such as the Child-Pugh Score.

Answer 241

Marker of viral replication and thus ACTIVE infection. Appears within 6 weeks of infection Disappears by 3 months after

Answer 242

Marker of previously cleared infection OR vaccination

Answer 243

Marker of a high degree of viral replication (infectivity)

Answer 244

Marker of natural immunity to Hep B

Answer 245

Non-specific marker of current / previous infection

Answer 246

Infection within the last 6 months

Answer 247

= The best marker of viraemia

Answer 248

HBsAg / HBeAg & PCR positive Liver Transaminases negative (transaminases will be raised in any active disease)

Answer 249

Vaccination involves injecting the hepatitis B surface antigen. Therefore there should only be evidence of surface antigen immunity (HBsAb)

Answer 250

PRE-ICTERIC PHASE: - 1-2 week prodrome – malaise, arthralgia, headache, anorexia - Classic aversion to cigarette smoke - Vague RUQ pain ICTERIC PHASE: - Patient becomes jaundiced – with associated pale stools and dark urine (intrahepatic cholestatic jaundice) - Pruritis - May be associated with lymphadenopathy and hepato-splenomegaly. Hep A and C often cause very mild or no symptoms Extra-hepatic features are more common in Hep B

Answer 251

Presents after a binge with jaundice, RUQ pain and systemic upset. May be signs of chronic liver disease (acute on chronic presentation) Bilirubin, prothrombin time and hepatic encephalopathy predict survival (combined to form the “discriminant function”) AST:ALT ratio >2.0 suggests alcoholic liver disease.

Answer 252

Most commonly presents as chronic hepatitis, but up to 40% of patients get acute hepatitis with jaundice. The chronic form presents insidiously: - Generally in women with non-specific symptoms of fatigue, arthralgia, fevers and weight loss. Age peaks are at 15-25 or perimenopausal years. Associated with other autoimmune conditions - Most commonly primary biliary cirrhosis - Primary sclerosing cholangitis - IBD

Answer 253

High transaminases and IgG levels Negative viral serology High tires of autoantibodies (non specific – e.g. ANA) Final diagnosis is with a liver biopsy.

Answer 254

Often asymptomatic unless complications (e.g. cirrhosis) develop Can only be diagnosed when serum ALT levels are elevated for >6 months => E.g. on follow-up from acute viral hepatitis diagnosis.

Answer 255

Start prednisolone 30mg OD Add Azathioprine 1mg/kg/day after TPMT assays If there are falls in transaminases, gradually reduce the prednisolone dose to maintain the fall. Long-term therapy with low-dose prednisolone (5-10mg) and azathioprine is then recommended => Bone protection plus monitoring required

Answer 256

Have a low threshold for screening patients with RFs for acquiring HBV Notify Public Health (it is a notifiable disease) Refer to gastroenterology, hepatology or infectious diseases for specialist management Lifestyle: - Stop smoking and alcohol - Education about reducing transmission and informing potential at risk contacts The acute episode is treated with supportive therapy and alcohol avoidance (95% will recover and develop immunity) 1st line management of chronic hepatitis is with SC peginterferon alfa-2a for 48 weeks.

Answer 257

Very specialist area of management – Refer to gastroenterology, hepatology or infectious diseases There are new drugs on the market that have replaced PEG interferons

Answer 258

- Chronic hepatitis - Cirrhosis - Suspected neoplastic disease - Storage diseases - Unexplained hepatomegaly

Answer 259

- Prolonged PT - Platelet count <80 - Ascites - Extrahepatic cholestasis

Answer 260

A newer alternative = fibroscan (transient elastography), which allows the liver “stiffness” to be measured non-invasively. Other non-invasive tests exist = MR elastography, serum biomarker tests.

Answer 261

= volume that has been exhaled at the end of the 1st second of forced expiration (Typically, over 70-80% of the FVC will be expired in the first second)

Answer 262

= forced vital capacity; the volume that has been exhaled after a maximal expiration following a full inspiration. (usually around 5L)

Answer 263

= Tidal Volume; the volume of air entering and leaving the lung with each normal breath

Answer 264

Both measures of gas transfer KCO = Diffusion capacity of the lung per unit area for CO. TLCO = Diffusion capacity of the total lung capacity for CO. Decreased TLCO /KCO indicate an issue with gas exchange, which can be due to either ALVEOLAR disease or VASCULAR disease. => This rules out chest wall/ diaphragm pathology.

Answer 265

Normal (or increased FVC) Reduced FEV1/FVC

Answer 266

Reduced FVC Normal (or increased) FEV1/FVC

Answer 267

= chronic dilation of the airways, leading to chronic inflammation/infection.

Answer 268

SYMPTOMS: * Recurrent cough, with copious amounts of infected sputum. * Intermittent haemoptysis (can be the only symptom). * Persistent halitosis * Dyspnoea * Recurrent febrile episodes and episodes of pneumonia SIGNS * Clubbing * Coarse inspiratory crackles over infected areas (typically bibasal) * Wheeze * Often low BMI, due to high energy demands

Answer 269

Idiopathic = most common Otherwise: - Post-infective – TB, measles, pertussis, pneumonia - CF - Bronchial obstruction – tumour/FB - Allergic broncho-pulmonary aspergillosis - Ciliary dyskinetic syndromes – Kartagener’s syndrome, Young’s syndrome - Immune deficiency – IgA, hypogammaglobulinaemia - CTDs – 1/3rd of RA patients develop bronchiectasis.

Answer 270

Any bronchi may be involved, but most commonly at the lung bases. Airways are dilated, with purulent secretions and chronic inflammation in the wall with inflammatory granulation tissue => Granulation tissue can bleed, leading to haemoptysis. With repeated exacerbations, there can be fibrous scarring, leading to respiratory failure.

Answer 271

Sputum culture => Atypical organisms CXR - Cystic shadowing CT => To assess distribution of disease; => Can see dilated airways with “signet ring” sign. Spirometry => Obstructive pattern => Reversibility should be assessed. Other tests to look for cause => E.g. serum immunoglobulins, CF sweat test, aspergillus precipitins

Answer 272

Atypical organisms Most common organism is haemophilus Pseudomonas, Klebsiella and Strep pneumoniae are also common

Answer 273

Assess for rare but treatable causes (e.g. immune deficiencies) Smoking cessation Chest Physiotherapy => Inspiratory muscle training Postural drainage – twice daily ABX for exacerbations => According to known sensitivities => Constant rotating ABX in severe disease Immunisations Bronchodilators can be useful in some cases Surgery is rarely indicated (as the disease is rarely confined to one lobe). => Lobectomy used to be common

Answer 274

Lung cancer Previously Bronchiectasis (less common now) Chronic lung abscess / TB Fungal infections – life-threatening haemoptysis due to aspergillus.

Answer 275

= Systemic non-caseating granulomatous disease. Most commonly affects the lungs, mediastinal lymph nodes, and skin. Typically occurs in females, aged 20-40 Presents as subacute illness, with non-specific features of malaise, arthralgia, etc. Pulmonary manifestations lead to fibrosis. Sarcoidosis can also lead to glomerulonephritis, cardiomyopathy, arthritis, cranial nerve lesions and erythema nodosum.

Answer 276

The acute form is usually self-limiting (2 months to 2 years) but it can present as a chronic insidious disease, with progressive dyspnoea. Tx: - Simple analgesia and NSAIDs - Occasional corticosteroid courses if there is progressive lung fibrosis.

Answer 277

1. Asthma 2. Extrinsic Allergic Alveolitis (EAA) – malt worker’s lung 3. Allergic Bronchopulmonary aspergillosis 4. Aspergilloma 5. Invasive Aspergillosis

Answer 278

More common in asthmatics and CF patients Type I and II reaction, giving asthma-like symptoms with a productive cough Needs steroid Tx

Answer 279

= fungal ball formation within pre-existing lung cavities (e.g. TB) May be asymptomatic, cause general malaise/weight loss or torrential haemoptysis. Tx = Single lesions may be resected.

Answer 280

Affects immunocompromised individuals Needs aggressive Tx with antifungals Mortality is high

Answer 281

Autosomal recessive inheritance Caucasians have a carrier frequency of 1 in 25 Due to a mutation in the cystic fibrosis transmembrane conductance regulator (CTFR) gene on chromosome 7, position 508. Genetic screening is available for the 4 most common mutations, and this identifies 90% of CF cases.

Answer 282

point deletion (DF508) This codes for a cAMP-regulated chloride cannel present on multiple epithelial surfaces (predominantly in the pancreas and respiratory tract).

Answer 283

mutation in the CTFR gene leads to abnormally thick secretions, this leading to pancreatic insufficiency and recurrent chest infections.

Answer 284

Recurrent childhood chest infections FTT Breathlessness and haemoptysis develop in later years as progressive bronchiectasis develops. Spontaneous PTX is common Most will have chronic sinusitis and many will have nasal polyps Respiratory failure and cor pulmonale can eventually develop due to scarring of the pulmonary vasculature.

Answer 285

initially mainly caused by S. aureus, Haemophilus influenza and gram-negative bacilli. Later, pseudomonas predominates (this is associated with poor prognosis).

Answer 286

Meconium ileus is common at birth Steatorrhoea due to pancreatic dysfunction, associated with malabsorption Increased frequency of gallstones & peptic ulceration. Cirrhosis sometimes develops in older patients.

Answer 287

Clubbing Infertility in most males (congenital absence of vas deferens rather than increased viscosity) Subfertility in females DM Rickets/osteomalacia (due to vitD deficiency)

Answer 288

Bloods: - FBC, U&Es, LFTs, clotting Sodium sweat test - Levels >70 mmol/L are characteristic Annual diabetes screening Sputum cultures CXR => Hyperinflation, evidence of bronchiectasis. Abdo USS => Fatty liver/cirrhosis => Chronic pancreatitis Spirometry => Obstructive deficits

Answer 289

CHEST - Two parenteral ABX are used for exacerbations (to decrease resistance, often one with pseudomonal cover). - Experts may decide whether to employ regular ABX prophylaxis - Mucolytics (e.g DNase daily nebulisers) - Airway clearance devices (E.g. acapella) - Lung transplant (if resp. failure develops). GI - Pancreatic enzyme replacement (Creon) - Fat soluble vitamin supplementation (ADEK) - Liver transplantation for advanced cirrhosis OTHER - Tx of diabetes - Fertility treatment - Genetic counselling. + disease modifying drugs?

Answer 290

Orkambi: - Used for patients with homozygous DF508 - Lumacaftor increases the number of CFTR proteins transported to the cell surface - Ivacaftor potentiates those already at the cell surface to increase the probability that the channel will be open Symkevi: - Can also be used for heterozygous DF508 patients.

Answer 291

In BBB, the depolarisation wave reaches the septum normally, so the PR interval is normal (in contrast to complete heart block). Delayed depolarisation of the ventricles thus leads to wide QRS (>120ms or 3 small squares)

Answer 292

The septum is depolarised from the left side as normal As it takes longer for excitation to reach the right ventricle, this depolarises after the left, causing a second R wave. RBBB is best seen in V1 with an "RSR pattern" Delayed overall conduction time to the RV extends the QRS duration to > 120 ms No specific Tx is needed for RBBB, but consider underlying ASD / PE.

Answer 293

conduction delay means that impulses travel first via the right bundle branch to the RV, and then to the LV via the septum Delayed overall conduction time to the LV extends the QRS duration to > 120 ms The overall depolarisation vector from the right to left ventricle produces tall R waves in lateral leads (I, V5-6) and deep S waves in the right precordial leads (V1-3). The delay between activation of the RV and LV produces the characteristic "M-shaped" R wave seen in lateral leads -- If LBBB is present, no further interpretation of the ECG is possible. => If asymptomatic, consider aortic stenosis. => If chest pain, LBBB = STEMI as you cannot prove otherwise

Answer 294

= abnormal conduction from the SAN to the ventricles.

Answer 295

= Fixed, prolonged PR-interval (>5 small squares or 1 big square) The prolongation remains fixed in length, and P-waves remain associated with QRS complexes 1st degree Heart Block is not itself pathological, but it can indicate: - Coronary artery disease - Acute rheumatic fever - Electrolyte disturbances - Digoxin toxicity.

Answer 296

Excitation intermittently fails to pass through the AVN or bundle of His. PR-interval progressively elongates, eventually culminating in the non-conduction of one P-wave, before the cycle begins again with a minimally-prolonged/normal PR interval. Often no specific treatment needed for this type.

Answer 297

Excitation intermittently fails to pass through the AVN or bundle of His. Intermittent conduction and non-conduction of P waves without PR-interval prolongation (can be no pattern, or fixed ratio e.g. “2:1”, “3:1”, etc. ) This type of block will need permanent pacing due to high risk of asystole.

Answer 298

= complete heart block There will be total dissociation between atrial and ventricular activity => NO conduction between atria and ventricles => ventricles are excited by a slow escape mechanism randomly Can occur acutely following MI, or be a chronic state. Tx --> Pacing is generally always required due to high risk of asystole.

Answer 299

Occurs in young people where heart rate changes with respiration – R-R interval changes progressively on a beat-beat basis.

Answer 300

HR <60 Can be associated with athletic training, fainting attacks, hypothermia, hypothyroidism. Can also occur immediately after MI

Answer 301

HR >100 Can be associated with exercise, fear, pain, haemorrhage or thyrotoxicosis

Answer 302

QRS complex is normal – depolarisation spreads to the ventricles in the usual way via the bundles. Sinus rhythms give a normal P wave Atrial rhythms give an abnormal P wave Junctional rhythms (AVN) will not show P waves.

Answer 303

wide (slower spread of depolarisation through the ventricles) and abnormal QRS complexes.

Answer 304

A slow, protective rhythm initiated by a focus in the ventricles if the SAN fails or conduction is completely blocked ~20 - 40 bpm

Answer 305

A-E, treat reversible causes Assess for adverse features and risk of asystole => Adverse features – shock, syncope, heart failure, myocardial ischaemia => Risk of asystole – recent asystole, Mobitz II or complete heart block If none of these features are present, continue to observe and monitor. If any of these features are present, initiate treatment and seek expert help => Atropine 500 mcg IV; repeated up to a maximum of 3mg. Cardiology may then initiate transcutaneous pacing prior to more definitive pacing of the heart.

Answer 306

If any part of the heart depolarises quicker than it should, and this is accompanied by an extra heartbeat, this is called an extrasystole. Atrial extrasystoles have an abnormal P wave Junctional extrasystoles have no P wave => Normal QRS complexes in both Ventricular extrasystoles have a wide QRS that can take virtually any shape. These are common and usually of no importance, however, if they occur early in the T wave of a preceding beat, they can induce a ventricular fibrillation.

Answer 307

the atria depolarise faster than 150/min => P waves are often superimposed on the previous T waves. The AV node can only conduct atrial discharge rates of up to 200/min, so above this “atrioventricular block” occurs and some P waves are not followed by QRS complexes.

Answer 308

A-E resuscitation, asses for adverse features. => Synchronised DC cardioversion if any adverse features. If irregular rhythm / atrial flutter – treat as AF If regular, first attempt vagal manoeuvres: => Carotid sinus massage / Valsalva manoeuvre => These lead to vagal stimulation of the SAN/AVN, causing decreased SAN discharge and increased AVN delay. If unsuccessful, IV adenosine. => 6mg initially, 12mg if no effect, then another 12 mg bolus. Electrical cardioversion if this is not successful. Secondary prevention is indicated with beta-blockers

Answer 309

Carotid sinus massage / Valsalva manoeuvre => These lead to vagal stimulation of the SAN/AVN, causing decreased SAN discharge and increased AVN delay.

Answer 310

Wide, abnormal QRS seen in all 12 leads. Potential to transform to VF, so requires urgent treatment Management: - If systolic BP <90mmHg, chest pain, heart failure or rate >150 – immediate electrical cardioversion - If absence of these signs – amiodarone 300mg loading dose over 30 minutes => Electrical cardioversion if this fails

Answer 311

No QRS can be identified and the ECG is totally disorganised The patient will usually have lost consciousness Manage as per the cardiac arrest protocol.

Answer 312

Irregular baseline with no P waves The AVN is bombarded and thus will depolarise irregularly, leading to ventricular contraction at an irregular rate. => Usually 450-600 atrial contractions / minute => Normal QRS as conduction from the AVN is not abnormal AF can be asymptomatic, or present with dyspnoea, palpitations, syncope, chest pain or stroke / TIA If no abnormalities are seen on ECG, 24-hour ambulatory ECG monitoring or an event recorder can be used to detect paroxysmal AF.

Answer 313

If presenting symptomatic with haemodynamic instability – emergency electrical cardioversion and immediate anticoagulation. If haemodynamically stable: 1. Rate control 2. Rhythm control 3. Anticoagulation

Answer 314

Generally 1st line Beta-blocker (bisoprolol) or RL CCB (verapamil / diltiazem) are the agents used. => CCBs are CI’d in heart failure; => Beta-blockers are CI’d in asthma Therapeutic target is 60-80 bpm at rest If the symptoms are not controlled with one drug, combination therapy can be used.

Answer 315

May be indicated in younger patients with new onset AF (<48h) and evidence of a reversible cause (e.g. chest infection), or the AF is causing heart failure. Cardioversion can be pharmacological or electrical Pharmacological options include flecanide and amiodarone. Cardiologist referral is generally required.

Answer 316

Heparin at initial presentation (if no contraindications / not already anti-coagulated) Then assessment of the need for long-term anticoagulation using the CHA2Ds2VAsc tool to assess stroke risk => Anticoagulation should be considered for anybody with a score of 2 or more => The HASBLED tool should be used to assess the risk of major bleeding. Either warfarin or a DOAC can be used according to patient preference (target INR 2-3) If an anticoagulant is contraindicated, offer DAPT (aspirin and clopidogrel), as one antiplatelet alone is not sufficient.

Answer 317

Cardiac – HTN, valvular heart disease, heart failure, ischaemic heart disease. Respiratory – chest infections, PE, lung cancer Systemic – excessive alcohol intake, thyrotoxicosis, electrolyte depletion, infections, DM. Consider assessment for these with FBC, TFTs, U&Es, glucose, ECG (old infarction), echo and CXR.

Answer 318

If the atrial rate is above 250 / min and no flat baseline between P waves exists, atrial flutter is present. => Classic “sawtooth” baseline. Can be thought of as similar to AF, in that the normal coordination of the atria are lost, however some element of synchronicity still exists. Generally treated as per AF.

Answer 319

Some people have an accessory conduction pathway, causing the action potential to bypass the AVN. This triggers early depolarisation of part of the ventricle (seen as a Delta Wave on the ECG) The second part of the QRS is normal as the bundle of His conduction catches up The ECG s in sinus rhythm but there is right axis deviation, short PR interval and widened QRS with a delta wave of pre-excitation. The only clinical importance is that it can cause paroxysmal tachycardia

Answer 320

Receives deoxygenated venous blood from the SVC, IVC and coronary sinus. Pumps blood though the right atrioventricular orifice (guarded by the tricuspid valve) separates the RA and RV. Forms the right border of the heart.

Answer 321

Receives deoxygenated blood from the right atrium Pumps blood through the pulmonary orifice (guarded by the pulmonary valve), into the pulmonary artery. It forms the majority of the anterior border of the heart.

Answer 322

Receives oxygenated blood from the four pulmonary veins Pumps blood through the left atrioventricular orifice (guarded by the mitral valve) into the left ventricle The left atrium forms the posterior border (base) of the heart

Answer 323

Receives oxygenated blood from the left atrium Pumps blood through the aortic orifice (guarded by the aortic valve) into the aorta.

Answer 324

Initially branches to yield the left anterior descending (LAD) artery (also “anterior interventricular artery”) Also gives off the left marginal artery (LMA) and the left circumflex artery (Cx). In ~20-25% of individuals, the left circumflex artery contributes to the posterior interventricular artery (PIv). Typically supplies: - The left atrium - Most of the left ventricle - Part of the right ventricle - Most of the IV septum – usually anterior two thirds (including AV bundle) - The SA node – approx. 40% of people

Answer 325

Branches to form the right marginal artery (RMA) anteriorly. In 80-85% of individuals, it also branches into the posterior interventricular artery (PIv) posteriorly. Typically supplies: - The right atrium - Most of the right ventricle - Part of the left ventricle - Part of the IV septum – usually posterior third - SA Node – approx. 60% of people - AV Node – approx. 80% of people

Answer 326

The coronary sinus runs from left to right in the posterior part of the coronary sulcus. The coronary sinus receives the great cardiac vein at its left end and the middle and small cardiac veins at its right end

Answer 327

represents atrial depolarisation Normally <3 small squares

Answer 328

= the distance between the start of the P wave and the start of the QRS complex it represents atrial depolaristation and the delay at the AV Node. Normal duration = 3-5 small squares

Answer 329

represents ventricular depolarisation. Normal duration – <3 small squares Normally positive in I, II, V4-V6; negative in aVR, V1 and V2

Answer 330

represents the whole ventricular action potential normal to be slightly longer in women This needs rate-correcting (QTc)

Answer 331

1. Patient identification + indication for ECG + calibration 2. General Impression 3. Rate 4. Rhythm 5. Axis 6. P-waves (present / absent) 7. P-R Interval (normal / prolonged / shortened) 8. QRS complexes (narrow / broad) 9. ST segments 10. T waves 11. QT Interval

Answer 332

1. Normal Axis => I, II and III all point up 2. Left axis deviation (“leaving”) => I up, II and III down - often associated with essential hypertension or valvular heart disease 3. Right axis deviation (“reaching”) => I down, II and III up - often associated with COPD and pulmonary hypertension.

Answer 333

Is the J-point of the ST segment elevated? must be by at least: * 1mm in the limb leads * 2mm in the chest leads must occur in 2+ adjacent leads => indicates STEMI

Answer 334

Any depression >0.5mm in 2+ leads is abnormal Indicates ischaemia.

Answer 335

Tall – at least ½ the amplitude of the preceding QRS complex Tented – look as if they’ve been pinched from above - i.e. a pointed peak, narrow base Caused by hyperkalaemia.

Answer 336

This is normal in Lead aVR (where everything should be negative) can be a normal variant in Leads V1 and III T-wave Inversion in other leads is a non-specific sign for Ischaemia, BBBs, PE, Hypertrophic Cardiomyopathy (HCM) etc.

Answer 337

a non-specific sign of ischaemia or of electrolyte imbalance (e.g. Hypokalaemia)

Answer 338

Can be either: - autosomal dominant (more common, less severe) - autosomal recessive.

Answer 339

Both kidneys are gradually replaced by enlarging fluid-filled cysts, compressing the parenchyma out of existence. Presentation: - Systemic HTN - CKD - Abdominal swelling (due to very large kidneys bilaterally) Renal failure generally occurs later in life, after the genes are passed on. Cysts also occur in the liver, lungs, pancreas (but without symptoms).

Answer 340

Rarer Earlier in onset Runs a more malignant course, with chronic renal failure earlier in life. Cysts in the liver lead to portal HTN and fibrosis

Answer 341

As for CKD, but with screening for berry aneurysms.

Answer 342

The glomerulus creates three layers for substances to pass through: 1. Fenestrated capillary epithelium 2. Basement membrane 3. Visceral layer – formed by interdigitating podocytes. This creates a “sieve” that allows small, charged ions through, yet will not allow the transport of proteins or blood.

Answer 343

injury to the glomerulus, caused by an immunological attack, by an antibody or T cell attacking an antigen in the glomerulus. This may be primary or secondary (acquired/deposited) Capillary - Endothelial cell proliferation => bigger fenestra - Capillary wall necrosis - Glomerulosclerosis – scarring in the mesangium leading to fenestra and capillaries being pulled apart. Basement Membrane - Thickened membrane – leading to structural distortion and thus becomes more permeable. Tubules - Deposition of cells in Bowman’s space.

Answer 344

N – neoplasm S – SLE A – amyloid I – Infection D – Diabetes HSP – Henoch Schoenlein Purpura

Answer 345

GLOBAL – whole glomerulus is diseased SEGMENTAL – small patches of one glomerulus are damaged in a “patchy” fashion DIFFUSE – affecting >50% of glomeruli FOCAL – affecting <50% of glomeruli

Answer 346

1. Proteinuria (at least 3.5 g/day) 2. Hypoalbuminaemia (<30g/L) 3. Oedema (due to decreased oncotic pressure and water retention). => Oedema typically occurs peri-orbitally and peripherally in limbs.

Answer 347

Investigate as per any suspected glomerulonephritis Tx: Diuretics, salt/water restriction and ACEIs to reduce proteinuria Anticoagulation if immobile, due to risk of thrombosis Treat the cause.

Answer 348

most common primary causes: - Minimal change nephropathy - Membranous glomerulonephritis - Proliferative glomerulonephritis Secondary causes may be bacterial/viral infection, drugs, neoplasm.

Answer 349

Renal loss of thrombo-regulatory proteins or lipo-regulatory proteins may lead to hyperlipidaemia or venous thrombosis.

Answer 350

Tetrad of: 1. Haematuria + red cell casts (can be microscopic) 2. Oliguria 3. Proteinuria (can be less than 3.5g) 4. HTN

Answer 351

NEPHROTIC - non-proliferative NEPHRITIC - proliferative (increased cell numbers as well as damage to the basement membrane)

Answer 352

Common primary causes: - IgA nephropathy - Goodpasture’s disease Secondary causes are commonly SLE/HSP.

Answer 353

Bloods – FBC, U&E, CRP, culture Urine dip to r/o infection Urine MCS for red cells/red cell casts/ Bence-jones protein Urine protein/creatinine ratio to quantify protein loss. Nephritic screen to look for causes. Renal USS Renal biopsy to confirm the cause in all adults

Answer 354

generally used instead of 24-hour urinary protein estimation, as it is more convenient and equally accurate. The amount of protein in mg per mmol of creatinine equates to the amount of protein excreted in over 24 hours Random protein:creatinine ratios >300mg/mmol are considered “nephrotic range” Ratios of 50-100 mg/mmol are considered significant proteinuria and should be repeated with an early morning sample.

Answer 355

= IgA nephropathy presents with nephritic syndrome Renal biopsy demonstrates IgA/C3 deposits Mx: - Supportive - 20% progress to ESRD over 20 years – steroids may slow the decline in renal function.

Answer 356

The most common cause of glomerulonephritis in children (75%) Characterised by normal light microscopy and negative immunofluorescence Electro-microscopy will show fusion of podocyte foot processes. Tx: - Oral steroids - Cyclophosphamide if relapsing. - 99% of cases resolve in 4-6 weeks if treated with steroids (adults may need longer courses).

Answer 357

Mostly idiopathic Diagnosed on biopsy => Global diffuse glomerulonephritis with IgG and C3 deposits

Answer 358

Idiopathic areas of segmental sclerosis, with IgM and C3 deposits Response to treatment is poor.

Answer 359

Presents with nephrotic or mixed nephrotic / nephritic syndrome Biopsy shows large glomeruli with a “double basement membrane” due to mesangial proliferation, giving a tramline appearance 50% develop ESRF in 10 years, and there is a high recurrence rate in transplants.

Answer 360

Patients present with nephritic syndrome 1-2 weeks following a sore throat / skin infection Biopsy shows a diffuse proliferative GN with IgG and C3 deposits, although there is no need to biopsy in typical cases. Bloods: - Raised ASOT / anti DNAase B - Reduced complement levels

Answer 361

Typically in children aged 3-15 Present with symptoms of a systemic small vessel vasculitis (IgA deposition) and nephritic syndrome following an URTI

Answer 362

Diagnosis is usually clinical, confirmed with positive immunofluorescence in skin/renal biopsy (IgA).

Answer 363

Purpuric rash on extensor surfaces Polyarthritis Abdominal pain (due to GI bleeding) Scrotal/scalp swelling Glomerulonephritis (indistinguishable from IgA nephropathy).

Answer 364

Attacks are usually self-limiting If there are relapses/evidence of progressive renal involvement, then corticosteroids are indicated.

Answer 365

Anti-glomerular basement membrane (anti-GBM) antibodies recognise an epitope on type IV collagen, present in the glomerular basement membrane. Presents with: - Haematuria and a rapidly progressive glomerulonephritis - Pulmonary haemorrhage leading to haemoptysis and breathlessness.

Answer 366

CXR will show pulmonary shadowing Renal biopsy will show linear IgG deposition along the glomerular basement membrane.

Answer 367

= plasma exchange and corticosteroids +/- cytotoxics.

Answer 368

Leads to focal segmental glomerulonephritis, with appearance overlapping with IgA nephropathy They are often ANCA positive.

Answer 369

= Glomerulonephritis rapidly leading to ESRF, presenting with signs of renal failure and systemic disease. Causes: - Immune complex diseas (e.g. SLE / endocarditis / IgA nephropathy). - Vasculitis (e.g. HSP, Wegener’s, Churg-strauss syndrome, etc.) - Goodpasture’s disease Management: - Aggressive immunosuppression (high dose steroids and cyclophosphamide). - Prognosis depends on how early treatment is initiated.

Answer 370

The tracts by which sensory information from a peripheral nerve is transmitted to the cerebral cortex. Consists of: - Dorsal columns - Lateral Spinothalamic Tract - Ventral spinothalamic tract

Answer 371

Transmit pain, temperature, and light touch to the thalamus. Decussates at the spinal level.

Answer 372

Transmit deep touch, proprioception, and vibration to the parietal cortex. Decussates in the brainstem.

Answer 373

Transmits motor axons from the motor cerebral cortex to the spinal cord. Decussates in the brainstem.

Answer 374

A to E => High C-spine lesions can lead to a total/partial loss of respiratory function. Determine the mechanism of injury Physical Examination: => Vision, palpation of vertebral column, neurological exam. Imaging

Answer 375

AP / lateral/ C2 open mouth (peg view) XR (if the C-spine cannot be cleared clinically) CT C-spine if - Already having head/other body CT - If X-Rays are suspicious - If intubated/rapid diagnosis required. Whole spinal X-ray if one spinal fracture identified.

Answer 376

Any trauma patients with LoC need C-spine stabilisation If there are signs of neurological deterioration, urgent CT head to T4/5 should be performed. If there are not – cervical, thoracic and lumbar spine XR is required. Spinal precautions can be ceased if a consultant radiologist reviews the above imaging and there are no signs of an abnormality; as well as no clinical signs suggestive of a spinal cord injury.

Answer 377

If GCS is 15 and the patient is stable, follow the “Canadian C-spine Rules” if spinal injury is a concern. If the patient is >65, has paraesthesia in the extremities or there was a dangerous mechanism => radiography. If not, then there are 5 factors which will allow attempt to clinically clear the C-spine. 1. Simple rear-end RTA 2. Sitting position in ED 3. Walking at any time 4. Delayed onset of neck pain 5. Absence of C-spine tenderness If none of these factors are present, then radiography is required. If one or more of these criteria are satisfied, attempt to clear clinically: * Ask the patient to rotate neck 45o to left and right * If the patient can do this, the C-spine can be considered “cleared” without radiology. If there is clinical uncertainty, it is always better to err on the side of caution and get radiology input.

Answer 378

- Neurogenic shock - Respiratory insufficiency - Quadriplegia - Anaesthesia below affected level - Loss of bladder/bowel sphincter tone - Sexual dysfunction - Horner’s syndrome may also be present

Answer 379

- Paraplegia - Anaesthesia below affected level - Loss of rectal/bladder sphincter tone. - Sexual dysfunction

Answer 380

A unilateral lesion of the spinal cord will cause Brown-Sequard Syndrome: => Ipsilateral reduced power (CST) / vibration & proprioception (DC) => Contralateral reduced pain/temperature/light touch (STT) This can occur in trauma or transverse myelitis (MS)

Answer 381

Tingling, numbness, electric-shock like syndromes Clumsiness O/E: - Sensory ataxia - Loss of proprioception, - Loss of vibration sense - Loss of 2-point discrimination below the level of the lesion.

Answer 382

Demyelinating disease – e.g. MS, B12 deficiency, etc. External compression – e.g. tumours, mechanical degeneration of cervical spine. Occlusion of posterior spinal artery.

Answer 383

Normal ICP is 0-10 mmHg.

Answer 384

Vasogenic – increased capillary permeability => Tumour, trauma, ischaemia, infection Cytotoxic – cell death Interstitial – obstructive hydrocephalus

Answer 385

Headache - Dull persistent ache, - Worse on lying, - Present on waking, - Worse by coughing/straining Vomiting Seizures Irritability

Answer 386

GCS deterioration Progressive dilation of the pupil on the affected side Cushing’s reflex Cheyne-Stokes respiration (Papilloedema is NOT an acute sign of raised ICP, it takes weeks to occur)

Answer 387

Elevate the head of the bed to 30-40 degrees If intubated, hyperventilate to reduce PaCO2 => Almost immediate reduction in ICP Mannitol => 0.2g/kg 20% IV over 15 minutes => Clinical effect after 20 minutes => Useful as a temporary measure prior to definitive management Corticosteroids: => Only useful for oedema around tumours Fluid restriction Consider monitoring ICP (surgically implanted extradural catheter) Make diagnosis and treat the cause

Answer 388

Hyperventilation if intubated Mannitol Controlled hypothermia, CSF drainage Barbiturates.

Answer 389

The patient lies on their side, curled forward with knees to their chest (opens lumbar interspinous spaces). Alternative position = sitting forward, curled into a pillow (especially useful in obese patients). However, the opening pressure can only be measured if the head is at the same level as the lumbar spine (i.e. in lateral recumbent position).

Answer 390

The spine of L4 is identified. => Found at the level of the tops of the iliac crest. A LP needle is introduced obliquely above L4, parallel to the place of the spine, though the interspinous ligament. There is a slight “give” as the needle pierces the dura-arachnoid mater to enter the subarachnoid space. The cord has ended, so rare to pierce the dura mater of the cauda equina and cause nerve damage.

Answer 391

Diagnosis of meningitis/encephalitis Diagnosis of SAH => If clinically suspected but no abnormalities on CT Measurements of CSF pressure => Idiopathic intracranial HTN Therapeutic removal of CSF: => Idiopathic intracranial HTN Intrathecal drug administration Diagnosis of various conditions: => MS, neurosyphilis, Behcet’s disease

Answer 392

Post-LP headache Dry tap (correct position of needle but no CSF comes out) Infection Damage to spinal nerves – causing weakness/paraesthesia Coning of cerebellar tonsils.

Answer 393

Occurs in 30% Onset within 24 hours, resolution over 2 weeks. Constant bilateral dull ache. Worse when upright Treat with analgesics +/- blood patch (re-injection of the patient’s own blood to form a clot).

Answer 394

Suspicion of intracranial / spinal cord mass, or raised ICP. => This can lead to coning of the cerebellar tonsils => Any unconscious patient must have a CT prior to LP Overlying/local infection Congenital lesions in the area (e.g. meningomyelocele) Problems with haemostasis Haemodynamic instability.

Answer 395

Xanthochromia = yellow-ish colour of the CSF. Caused by bilirubin from RBC breakdown => RBCs in the CSF indicates there has been a SAH If the RBCs in the CSF are due to bleeding at the LP site, they will not have been degraded to bilirubin, so CSF will not be xanthochromic.

Answer 396

Moderately raised protein levels – less than 1 g/L Up to 50 lymphocytes / mm3 Oligoclonal IgG bands on electrophoresis.

Answer 397

= a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Thought to be auto-immune process - Symptoms occur 1-3 weeks after an infection - Infection may be trivial and unidentified - Campylobacter and CMV infections are well-recognised causes of severe GBS

Answer 398

Ascending paralysis, with loss of tendon reflexes Sensory loss is rare Usually affects the lower limbs initially Ascends and progresses over several days to weeks. Proximal muscle involvement is common – e.g. cranial nerves, respiratory muscles. Other complications: - VTE - Autonomic involvement – leading to BP lability / arrythmias

Answer 399

Supported by nerve conduction studies (showing slowed conduction) CSF protein is often also raised.

Answer 400

Severe cases progress rapidly over hours to days. Admit to HDU Some patients will require ventilator support. s.c. Heparin plus TED stockings High dose IV immunoglobulin (IVIG) within the first 2 weeks. => Reduce duration and severity of paralysis => Corticosteroids are of no use.

Answer 401

In mild cases, there is little disability before spontaneous recovery. Complete recovery occurs over months in 80-90% => Some may be left with residual weakness Mortality is very high in the acute phase – up to 10%

Answer 402

= degenerative disease of UMNs and LMNs in the spinal cord, cranial nerve motor nuclei and the cortex. There is NO sensory involvement. It is sporadic, with the cause unknown (although there are rare genetic forms). Peak onset is age 50-70

Answer 403

Amyotrophic Lateral Sclerosis Progressive Muscular Atrophy Primary Lateral Sclerosis Bulbar Presentation

Answer 404

Loss of spinal and brainstem LMNs, and cortical UMNS (giving both UMN and LMN signs) Progressive spastic tetraparesis and added LMN signs such as wasting and fasciculation. May be associated with fronto-temporal dementia Presentation: - LMN weakness – starting in the hands and progressing to upper arms/legs - UMN spastic weakness – starting in the legs and progressing to the arms - Bulbar palsy / pseudobulbar palsy O/E: => The classical sign is muscle wasting and fasciculation with brisk reflexes and up-going plantars. Sensory examination is normal

Answer 405

Loss restricted to spinal LMNs, giving purely LMN signs Painless wasting begins in the small muscles of the hands, and spreads. O/E – wasting and fasciculation is seen

Answer 406

Rare form of MND Disease confined to cortical UMNs, giving purely UMN signs Progressive tetraparesis

Answer 407

Bulbar symptoms with preservation of limb function in early stages. Poor prognosis due to early respiratory involvement

Answer 408

Diagnosis can be clinical in the presence of mixed UMN / LMN signs in multiple limbs, but investigations are usually useful to establish the diagnosis: - Bloods – r/o differentials - Spinal cord MRI – r/o myelopathy - EMG – evidence of denervation, can be diagnostic.

Answer 409

Should be managed by a specialist MDT Social and carer assessments are important Disease modifying therapy: => Riluzole – increases pre-synaptic glutamate release, can increase survival in ALS patients by an average of 3-4 months. Nutritional Support Respiratory Support => Overnight NIPPV if respiratory weakness is an issue (biggest prognostic benefit) Tx of complications (as per MS)

Answer 410

Remission of MND is not known Death is eventually from bronchopneumonia or ventilatory failure due to weakness of the respiratory muscles.

Answer 411

LMNs innervate ipsilateral muscles Signs: - Weakness - Wasting - Fasciculation - Hypotonia - Hyporeflexia

Answer 412

UMNs innervate contralateral muscles SIGNS: - Weakness (characteristically extensor weakness in UL, flexor weakness in LL) - No wasting - Hypertonia, spasticity - Hyperreflexia - Loss of fine motor movements - Pronator drift - Extensor plantar response - Clonus

Answer 413

Ventral horn pathology (MND, post-polio) Peripheral nerve pathology NMJ pathology (MG) Muscular pathology

Answer 414

Vascular – stroke Inflammatory – MS, MND Neoplastic – tumour Degenerative – Parkinson’s Infective – post-meningitis Drugs

Answer 415

LMN lesions cause ipsilateral facial weakness of all muscles of facial expression. UMN lesions cause contralateral facial weakness, but spare frontalis (as this received supranuclear innervation from both hemispheres) => Furrowing of the brow, eye closing and blinking are preserved

Answer 416

Separated from the parietal lobe posteriorly by the central sulcus and from the temporal lobe infero-posteriorly by the lateral sulcus Responsible for: * Higher intellect, * Personality, * Mood, * Social conduct * Language (dominant hemisphere side only).

Answer 417

Between the frontal lobe anteriorly and the occipital lobe posteriorly Separated from these by the central sulcus and parieto-occipital sulcus Contributes to the control of: * Language and calculation on the dominant hemisphere side * Visuospatial functions (e.g. 2-point discrimination) on the non-dominant hemisphere side.

Answer 418

Inferior to the frontal and parietal lobes, from which it is separated by the lateral sulcus. Involved with: * Memory * Language – this includes hearing as it is the location of the primary auditory cortex.

Answer 419

The most posterior part of the cerebrum Its inferior aspect rests upon the tentorium cerebelli, which segregates the cerebrum from the cerebellum The parieto-occipital sulcus separates the occipital lobe from the parietal and temporal lobes anteriorly. The primary visual cortex (V1) is located within the occipital lobe (hence it is responsible for vision)

Answer 420

Located at the back of the brain, immediately inferior to the occipital and temporal lobes, and within the posterior cranial fossa. It lies at the same level of and posterior to the pons, (these are separated by the fourth ventricle) Plays an important role in motor control. => In particular – coordination, precision and timing of movements, as well as in motor learning Each cerebellar lobe controls movement of ipsilateral limbs. The vermis (midline structure) maintains midline posture and balance.

Answer 421

Supplies medial surface of cerebral hemisphere, as far back as the peri-occipital sulcus

Answer 422

Supplies 2/3rd of the lateral surface of the brain Central branches supply the corpus striatum, thalamus and internal capsule.

Answer 423

Supplies the corpus callosum and cortex of occipital and temporal lobes. Central branches supply the optic radiation, subthalamic nucleus and thalamus

Answer 424

supplied by the vertebral and basilar arteries

Answer 425

= Olfactory Special sensory – smell from nasal mucosa

Answer 426

= Optic Special sensory – vision from retina

Answer 427

= Oculomotor Somatic motor – 4 of 6 extra-ocular muscles, levator palpebrae superioris. Visceral motor – pupil constriction

Answer 428

= Trochlear Somatic motor – superior oblique muscle

Answer 429

= Trigeminal Ophthalmic nerve (V1) – sensory to upper 1/3rd of face and cornea Maxillary Nerve (V2) – sensory to middle 1/3rd of face Mandibular Nerve (V3): - Sensory – lower 1/3rd of face - Motor – muscles of mastication

Answer 430

= Abducens Somatic motor – lateral rectus muscle

Answer 431

= Facial Somatic motor – muscles of facial expression Visceral motor – submandibular/sublingual glands; lacrimal gland Special sensory – taste from the anterior 2/3rd of tongue General sensory – skin of external acoustic meatus.

Answer 432

= Vestibulocochlear Special sensory – hearing and balance.

Answer 433

= Glossopharyngeal Somatic motor – swallowing Visceral motor – parotid gland Special sensory – posterior 1/3rd of tongue General sensory – external ear and pharynx

Answer 434

= Vagus Somatic motor – swallowing Visceral motor – parasympathetic innervation to smooth muscle of trachea, bronchi, GI tract and heart. General sensory – auricle and external acoustic meatus

Answer 435

= Spinal Accessory Motor – SCM and trapezius muscles

Answer 436

= Hypoglossal Motor – intrinsic/extrinsic muscles of tongue

Answer 437

Also the "bulb" => "bulbar palsy" = CN IX, X, XII

Answer 438

= excessive CSF within the cranium. High pressure then leads to dilation of the lateral ventricles +/- dilation of the 3rd and 4th ventricles. Can be either COMMUNICATING or NON-COMMUNICATING (or, very rarely, caused by CSF overproduction)

Answer 439

Most common type Due to blockage of the CSF pathways from the ventricles to the subarachnoid space.

Answer 440

Due to impairment of CSF reabsorption at the arachnoid vili along the dural venous sinuses. Usually precipitated by infection (particularly TB meningitis) or SAH

Answer 441

Patients with congenital malformations => E.g. stenosis of the aqueduct of Sylvius. Posterior fossa / brainstem tumours Post brain insult => E.g. SAH, head injury, meningitis

Answer 442

- Headache - Vomiting - Papilloedema - Cognitive Impairment - Ataxia - Bilateral pyramidal signs

Answer 443

CT to assess size of ventricles MRI if suspecting malformations / tumour

Answer 444

MEDICAL = to reduce CSF secretion / increase absorption - Only role is to delay surgical management - Acetazolamide, alone or in combination with Furosemide. SURGICAL: - Ventriculo-atrial or ventriculo-peritoneal shunting for progressive symptoms (Valves open at certain pressures to release CSF) - Endoscopic 3rd ventriculostomy is an alternative procedure for obstructive hydrocephalus. - Neurosurgical removal of tumours if appropriate

Answer 445

= the syndrome of enlarged lateral ventricles usually in the elderly associated with a classic triad: 1. Dementia (despite no signs of cortical atrophy on CT) 2. Urinary incontinence 3. Ataxia

Answer 446

Isolated CSF measurements are usually normal, but continuous monitoring may show intermittent periods of raised pressure.

Answer 447

Some patients respond to ventriculoperitoneal shunting, only indicated if they respond to trials of lumbar drainage.

Answer 448

= an autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest. Due to IgG autoantibodies against the ACh receptor located on the post-synaptic membrane of the motor end plates

Answer 449

IgG autoantibodies against the ACh receptor located on the post-synaptic membrane of the motor end plates This blocks synaptic transmission at the NMJ and prevents the acetylcholine from being able to stimulate the receptor and trigger muscle contraction These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane. (a small % of MG cases are caused by other antibodies against important proteins for the creation and organisation of the acetylcholine receptor)

Answer 450

There is a strong link with thymoma (a tumour of the epithelial cells of the thymus) ~25% with MG have thymoma.

Answer 451

Weakness and fatiguability that gets worse throughout the day. Classically affects: - Proximal limb muscles – fluctuating proximal weakness, more common in the upper limb. - Extra-ocular muscles – symmetrical diplopia and ptosis - Bulbar muscles – dysphagia/speech difficulties - Muscles of facial expression – weakness in facial movements Wasting and respiratory difficulties may occur after many years. The heart is not affected. Tendon reflexes are preserved.

Answer 452

Serum anti-AChR antibody titre Single fibre electromyography => Diagnostic – decreased responses to repeated stimulation TFTs and CT – for evidence of thymoma

Answer 453

Previously used in the diagnosis of MG Now rarely used due to risk of arrythmia IV injection of edrophonium (short-acting anticholinesterase) – will produce rapid, transient improvement in features. Cardiac monitoring and resuscitation should be available.

Answer 454

Avoidance of certain antibiotics that may exacerbate NM blockade – e.g. aminoglycosides Lifelong long-acting oral ANTICHOLINESTERASES => Neostigmine/pyridostigmine. CORTICOSTEROIDS for relapses: Starting in hospital, as risk of increasing weakness early on. Weakness of respiratory muscles can be life-threatening => Monitor FVC, May need ventilatory support => Severe cases will require IVIG / plasmapheresis Alternate-day regimen after discharge => Azathioprine may be useful as a steroid-sparing agent. Thymectomy => Performed at any age will increase the chance of remission

Answer 455

~15% of strokes = either intra-cerebral haemorrhage or SAH

Answer 456

As per haemorrhagic stroke At the bedside there is no reliable way to differentiate. => More likely to present with severe headache and coma

Answer 457

CT – haemorrhage will be seen immediately MRI – very reliable after 2 hours from symptom onset.

Answer 458

Stop and reverse any anticoagulation Intubate if GCS is 8 or less Lower BP to <140/90 within 1 hour => IV labetalol Maintaining adequate oxygenation and MAP Neurosurgical intervention may be required.

Answer 459

“Thunderclap” headache => Develops over seconds, devastating intensity, often occipital => Often comes on during times of transient HTN – such as physical activity or sexual intercourse. Vomiting: => Comes on after developing the headache. Photophobia Increasing drowsiness/coma Focal signs may point to the location of the lesion. => However, may just reflect raised ICP (false localising sign) or cerebral vasospasm due to the irritant effect of blood. O/E: - Neck stiffness - Positive Kernig’s sign – takes 6 hours to develop - Papilloedema (may be present); retinal haemorrhages.

Answer 460

The patient may have experienced an earlier “sentinel headache” before the thunderclap headache. due to a small warning lead from the offending aneurysm. Small bleeds may give few physical signs, but almost always a headache.

Answer 461

Berry Aneurysms (70%) Arteriovenous Malformations (10%) No lesion found (20%)

Answer 462

Developmental rather than congenital Develop in circle of Willis and adjacent arteries ACA = most common PCA – at bifurcation from ICA MCA – at bifurcation/trifurcation

Answer 463

- Polycystic kidney disease - FHx - Smoking - HTN - Connective tissue diseases

Answer 464

MASS EFFECTS => most common cause of painful 3rd CN palsy HAEMORRHAGE

Answer 465

Congenital collection of abnormal arteries/veins Have a tendency to rebleed if symptomatic once (10% will rebleed annually) Can also cause epilepsy

Answer 466

DEATH – 30% will die immediately RE-BLEED: => Aneurysms – the initial bleed may be fatal, however if vasospasm is sufficient then a clot can form; this usually holds for 3-4 days before re-bleeding. => AVMs – generally rebleed within a few years. HYDROCEPHALUS: Due to fibrosis in the CSF pathways CEREBRAL VASOSPASM: Can be severe, leading to delayed ischaemic damage.

Answer 467

Bloods: - FBC, U&E, LFT, ESR, clotting CT = initial Ix of choice - SAH/intraventricular blood usually seen within 48h LP – if CT normal - Should be done >12 hours after symptom onset - CSF will be xanthochromic (visual inspection sufficient for diagnosis). CT/MRI angiography – in all patients fit for surgery => To determine underlying vascular anatomy

Answer 468

4 weeks bed rest HTN control => Nimodipine – to prevent vasospasm (reduces mortality) – give to all if BP allows. IV fluids Analgesia, anti-emetics Stool softeners - to prevent straining Discuss with neurosurgery => Aneurysms may need to be coiled by interventional radiology or require neurosurgical clip => AVMs may require coiling or other neurosurgical intervention => Patients with hydrocephalus may need a shunt.

Answer 469

= collection of blood in the subdural space, following the rupture of a vein. Usually following head injury, but can occur spontaneously. Patients are often young

Answer 470

Patients are often young, post-head injury Often occurs in severe acceleration-deceleration injuries Present to hospital with a dilated pupil and NO lucid interval before decreased GCS

Answer 471

May occur spontaneously or after minor trauma. Can be bilateral Symptoms and signs of raised ICP, developing about 3 weeks after insult or start of bleed and often fluctuant: => Headache, drowsiness, confusion, focal neurological signs. Eventually stupor and coma due to coning.

Answer 472

CT head to confirm Craniotomy and early evacuation of the clot is required. These patients are often seriously ill even with early intervention. => Require ICU admission with intracranial pressure monitoring. High incidence of subsequent epilepsy, permanent neurological disability and high mortality.

Answer 473

- Head injury (acute) - Elderly (cortical atrophy stretches brittle veins) - Alcohol abuse - Other coagulopathies

Answer 474

CT head to confirm Chronic subdural haemorrhage may resolve spontaneously. Progress can be assessed with serial imaging, but neurosurgical input is required.

Answer 475

CT Acute SDH: - Classic CRESCENT-SHAPE with increased density, conforming to the contour of the skull. - May be accompanying midline shift and compression of ventricles. Chronic SDH: - Blood becomes more radiolucent (darker), and assumes a lentiform shape, similar to that of an extrdural haemorrhage.

Answer 476

Most common in young patients following minor assault or sporting injury. Blow is usually to the side of the head, enough to cause a fracture and associated tearing of the middle meningeal artery. Blood accumulates rapidly over minutes to hours in the extradural space.

Answer 477

Brief duration of unconsciousness, and then a LUCID recovery period. Progressive hemiparesis and stupor develops due to trans-tentorial coning. First there is an ipsilateral dilated pupil, then bilateral fixed dilated pupils. If untreated, there is hemiplegia and respiratory arrest.

Answer 478

CT => characteristic LENTIFORM shape Midline shift and compression of the ventricles as it enlarges.

Answer 479

EDH = lentiform SDH = crescent

Answer 480

Urgent neurosurgical referral => Burr hole to release pressure => Prognosis is very good if this is performed early. If very minor, may be managed conservatively with regular monitoring.

Answer 481

= an acute, focal neurological deficit of cerebrovascular origin that persists >24 hours.

Answer 482

85% Either due to: - Arterial embolus from a distant site - Arterial thrombosis in atheromatous carotid/vertebral/basilar artery - Systemic hypoperfusion (general circulatory problem)

Answer 483

MODIFIABLE HTN Hypercholesterolaemia Diabetes Smoking Alcohol Poor diet Low exercise Increased weight Use of oestrogen-containing OCPs NON-MODIFIABLE Age Family History Hypercoagulable states Non-white ethnicity AF

Answer 484

Family History Uncontrolled HTN Vascular abnormalities (aneurysms, AVMs, HHT) Coagulopathies/anticoagulant therapies Heavy recent alcohol intake. Illicit drug use (mostly amphetamines and cocaine) Trauma

Answer 485

Facial weakness – sparing forehead. Contralateral limb weakness/hemiplegia and loss of sensation. => At first flaccid, but over time reflexes return and become exaggerated, with extensor plantars. Higher Dysfunction Visual Disturbances Seizures (rare)

Answer 486

= Proximal MCA Occlusion Affecting the areas of the brain supplied by both the middle and anterior cerebral arteries Must have all three of: 1. Higher dysfunction (incl. decreased level of consciousness) 2. Homonymous hemianopia 3. Contralateral hemiplegia and/or sensory loss (>2 of face, arm, leg)

Answer 487

= distal MCA or ACA occlusion A less severe form of TACS, in which only part of the anterior circulation has been compromised. Requires 2 of the 3 TACS criteria.

Answer 488

= occlusion of lacunar branch of MCA leading to subcortical stroke There is no loss of higher cerebral functions (e.g. dysphasia). One of the following: - Pure motor symptoms - Pure sensory symptoms - Pure sensorimotor symptoms - Ataxic hemiparesis

Answer 489

Expressive aphasia = inability to express language despite intact comprehension Receptive aphasia = inability to understand commands, may have fluent but meaningless speech. Apraxia = difficulty in performing task, despite intact motor function. Asterognosis = inability to identify objects in both hands, despite intact sensation. Agnosis = inability to recognise objects/people/sounds/smells despite the specific sense intact and no memory loss. Inattention (neglect) = inability to attend to stimuli despite intact senses.

Answer 490

= PCA occlusion. There will be damage to the area of the brain supplied by the posterior circulation (e.g. cerebellum, thalamus, and brainstem). Presents as: - Cranial nerve palsy AND contralateral motor/sensory deficit. - Conjugate eye movement problems (e.g. nystagmus, double vision) - Cerebellar dysfunction - Isolated homonymous hemianopia

Answer 491

TACS PACS LACS POCS “Syndrome” describes indeterminate pathogenesis prior to imaging (e.g. TACS) => If confirmed infarct = TACI => If confirmed haemorrhage = TACH

Answer 492

HPC: - Exact time of onset - Speed of onset - Body parts affected - Seizure at onset? PMH: - Previous stroke/MI - AF - DM - Abscess - Tumour? DHx: - Anticoagulants - OCP SHx: - Alcohol abuse, Smoking, Illicit drug use

Answer 493

GCS NIHSS – national institute of health stroke scale: => 15-item neurologic examination stroke scale => Evaluates level of consciousness, language, neglect, visual field loss, extra-ocular movement, motor strength, ataxia, dysarthria, and sensory loss. => Gives rapid insight into location of the stroke and severity – identifying those who may benefit from thrombolysis. CVS: => Murmurs (endocarditis), BP, HR, signs of dissection Respiratory: => SpO2, RR, crackles Neurological: => UMN/LMN signs => CNS and cerebellar examination

Answer 494

15-item neurologic examination stroke scale Evaluates level of consciousness, language, neglect, visual field loss, extra-ocular movement, motor strength, ataxia, dysarthria, and sensory loss. Gives rapid insight into location of the stroke and severity – identifying those who may benefit from thrombolysis.

Answer 495

ADMIT TO STROKE WARD IF POSSIBLE BLOODS: => FBC, U&Es, glucose + HbA1c, lipids, clotting screen, ESR BRAIN IMAGING: - MRI = gold-standard due to higher resolution, but less availability. - CT = rapid and commonly used, mainly used to exclude haemorrhage. Early signs of infarct can be seen as loss of grey-white differentiation, sulcal effacement, loss of insular ribbon

Answer 496

within 1 hour if: - Considering thrombolysis - Bleeding risk/headache at onset - Decreased consciousness - Neck stiffness

Answer 497

A – E assessment => Always check glucose – hypoglycaemia is a common mimic. Withhold antiplatelet therapy until haemorrhage excluded => As soon as excluded, administer aspirin 300mg. If patient has had symptoms for over 30 minutes, but onset was within 4.5 hours – arrange THROMBOLYSIS. If thrombolysis is contraindicated – manage supportively on the ward, continuing 300mg aspirin daily for 2 weeks whilst implementing secondary prevention measures.

Answer 498

Check for contraindications first (must have lab blood results back) Alteplase 0.9 mg/kg as per clinical pathway within the hospital 10% bolus over 1 minute, remainder over 60 minutes.

Answer 499

- SALT – swallow assessment ideally within 2 hours - PT – relieve spasticity and prevent contractures; early mobilisation is vital. - OT - Nursing – SSKIN bundle, early nutrition required if NBM - LMWH anticoagulation started on day 3 post-ischaemic stroke - Ensure TED stockings are being worn.

Answer 500

Patient is closely monitored over 24 hours via cardiac monitor and has specific observations completed on stroke thrombolysis observation chart. If the patient develops severe headache, acute HTN, nausea or vomiting hen discontinue infusions and obtain emergency CT. Avoid catheterisation during the infusion Avoid aspirin or heparin for 24 hours. Avoid NG tube insertion for 1st 24 hours.

Answer 501

Identify and tackle lifestyle risk factors. => E.g. stop smoking, reduce alcohol, regular exercise, etc. Antihypertensive therapy = most important factor. => Start 2 weeks following stroke if elevated BP Antiplatelet therapy: => Aspirin 300mg for 2 weeks => Clopidogrel 75mg lifelong. Statin: => Offer from 48 hours post-stroke, regardless of cholesterol levels. Manage co-morbidities appropriately: => Good AF control / anticoagulation, good diabetes control => Carotid USS Assessment of social care needs (+/- home assessments and modifications) => Independent patients can often become more dependent after a stroke

Answer 502

Patients with normal license must not drive for 4 weeks following a stroke. After this period they may return to driving if clinical improvement is satisfactory, without needing to inform the DVLA.

Answer 503

Malignant MCA syndrome DVT / PE Aspiration & hydrostatic pneumonia Pressure sores Depression Seizures Incontinence Post-stroke pain

Answer 504

= Rapid neurological deterioration due to the effects of cerebral oedema following MCA territory stroke. High morbidity / mortality Mainly occurs in patients <60 Presentation – can be variable, high index of suspicion required: - Increased agitation / restlessness - Reducing GCS - Haemodynamic / thermal instability - Signs of raised ICP These patients require decompressive hemi-craniectomy

Answer 505

= an acute, focal neurological deficit of cerebrovascular origin that persists <1 hour, without signs of cerebral infarction on MRI scanning. Only diagnosed after resolution Can occur in brain, spinal cord or retina There is a very high risk of stroke within 4 weeks of a TIA.

Answer 506

= sudden, transient loss of vision in one eye. Often occurs in TIA of the retina, can be the first clinical evidence of ICA stenosis. Can also occur due to ocular disease or migraine.

Answer 507

Assess the patient’s immediate further stroke risk Immediate 300mg aspirin => Unless contraindicated, patient already anticoagulated or already taking aspirin 75mg daily. Consider admission if more than one recent TIA (crescendo TIA) or suspected carotid/cardio-embolic source Otherwise, arrange outpatient specialist TIA clinic assessment within 24 hours. => Can be within 7 days if TIA was >1 week ago. Give all people with suspected TIA and their family/carers information on the recognition of stroke and TIA and advise them to call 999 immediately if symptoms occur.

Answer 508

Recurrent TIAs within a short period of time AF, or TIA whilst anticoagulated.

Answer 509

Advise patient not to drive until seen by specialist in TIA clinic

Answer 510

Carotid artery doppler – to assess for carotid artery stenosis If stenosis is >50% on affected side related to symptoms, carotid endarterectomy is offered: => Reduced risk of further stroke/TIA by 75% Alternative = percutaneous luminal angioplasty +/- stenting.

Answer 511

As per stroke – will be initiated by secondary clinic Clopidogrel = antiplatelet of choice. (Aspirin and dipyridamole if clopidogrel is unsuitable)

Answer 512

= disease involving relapsing episodes of immunologically mediated (T-cell mediated) demyelination in the CNS, leading to neurological degeneration.

Answer 513

Areas of demyelination are termed plaques (containing chronic inflammatory cells) Best seen in certain locations: - Optic nerves - Angles of the lateral ventricles - Cerebellar peduncles - Brainstem - Dorsal and corticospinal tracts

Answer 514

Symptoms are related to the common areas of demyelination: - Optic nerve => visual disturbances - Corticospinal tract => UMN deficit - Dorsal tract => sensory deficit - Cerebellar peduncles => cerebellar signs - Brainstem => bladder/bowel/sexual dysfunction - Cognitive impairment (late) In all forms of MS, episodes of neurological deficit appear irregularly throughout the CNS in terms of anatomical site and time.

Answer 515

Optic neuritis is a common presenting feature Symptoms are: * blurring of vision over hours to days * Mild ocular pain (worse on movement) * Loss of colour vision O/E: * Decreased acuity and colour vision * Pink/swollen optic disc Diplopia is also common, due to brainstem involvement.

Answer 516

induce tingling sensations shooting down the arms/legs on neck flexion Due to posterior cervical demyelinating lesions in MS

Answer 517

MS symptoms are clinically worse during a fever, hot weather, or after exercise (as central conduction is slowed by increased body temperature)

Answer 518

Recurrence is unpredictable, with no clearly identified precipitating factors (although pregnancy / intercurrent illness may be implicated)

Answer 519

Primary Progressive MS => No clear-cut relapses/remissions Relapsing/remitting MS (80-90%) => Initial episodes resolve completely => Subsequent events usually result in some residual disability. => Patients eventually develop secondary progressive MS (steady progression without remission) Fulminating MS => Debilitating progressive deterioration from an early stage.

Answer 520

Clinically – two separate MS-like episodes of neurological dysfunction Diagnosis then conformed with MRI evidence of lesions

Answer 521

In primary care – NICE recommend doing: => FBC, U&E, LFT, ESR, TFT, glucose, calcium, B12 and HIV serology before referring to a neurologist. MRI => Will show lesions in 85% of patients with clinical disease => Lesions are not specific to MS, so clinical features are also required. CSF Examination: => Often unnecessary if MRI is diagnostic => Raised cell count and protein. => Electrophoresis shows oligoclonal IgG bands in 80% (non-specific) Visual Evoked Responses (VER): => Delayed occipital EEG reactions to visual stimuli are present in 95% of those with MS => Useful to demonstrate evidence of previous optic nerve lesions to demonstrate previous subclinical disease.

Answer 522

1. Investigate appropriately to r/o other causes (particularly infection) 2. Consider admission if relapse is severe or patient cannot meet their social care needs at home. 3. High-dose Corticosteroids: - Oral methylprednisolone 500mg o.d for 5 days. - Start as soon as possible in the attack - May reduce severity of attack, no effect on long-term outcome. 4. Assess whether any increase in social care is required. 5. Patient education

Answer 523

Inform that steroids likely to reduce attack severity and duration, but may cause temporary mental health effects (confusion, anxiety, depression, psychosis) Significant recovery can be expected in 2-3 months, but there may be some residual symptoms.

Answer 524

Patients should be under the care of a specialised MS MDT, with annual review. Lifestyle advice: - Regular exercise can be beneficial - Smoking cessation improves disease course Prompt recognition and treatment of any co-existing illness => Illness/fever can frequently exacerbate MS symptoms Assess for and appropriately manage complications Disease modifying therapy (initiated by specialist).

Answer 525

Average life expectancy from diagnosis = 20-30 years There may be a long latent period (15-30 years) from an episode of optic neuritis before further Sx occur Poor prognostic factors: - Increased age of presentation - Early cerebellar involvement - Loss of mental functions

Answer 526

= Central Scotoma

Answer 527

= Ipsilateral Monocular Vision Loss

Answer 528

= Bitemporal Hemianopia / Quadrantanopia Can get superior bitemporal quadrantanopia due to pressure from below the chiasm => E.g. pituitary tumour. Inferior bitemporal quadrantanopia is due to pressure from above the chiasm => E.g. craniopharyngioma, carotid aneurysm, meningioma.

Answer 529

= Contralateral Homonymous Hemianopia

Answer 530

= Contralateral Homonymous Quadrantanopia Temporal lesions = inferior fibres (superior retina) => superior homonymous hemianopia Parietal lesions = superior fibres (inferior retina) => inferior homonymous hemianopia

Answer 531

Homonymous hemianopia / quadrantanopia with Macular Sparing (macula gets blood supply from both PCA and MCA).

Answer 532

Motor speech function Located in inferior frontal gyrus, areas 44 + 45

Answer 533

Involved in understanding of the spoken word Located in superior temporal gyrus, area 22

Answer 534

= expressive aphasia, loss of ability to produce speech. Non-fluent – verbal output reduced Comprehension is good, repetition is poor

Answer 535

= receptive aphasia, loss of ability to understand speech Fluent – normal production of incorrect words Poor comprehension, poor repetition.

Answer 536

= Both expressive and receptive dysphasia

Answer 537

= disordered articulation / slurred speech, language remains intact

Answer 538

Bulbar palsy => LMN, high-pitched nasal speech Pseudobulbar palsy => UMN, “Donald duck” gravelly speech Cerebellar lesion => Slow, jerky/staccato, slurred speech Extrapyramidal lesions => Soft, indistinct, monotonous speech Myasthenia Gravis => Speech fatigues and dies away

Answer 539

= oculo-sympathetic palsy, caused by interruption of the sympathetic chain. 1. Unilateral pupillary constriction (miosis). 2. Partial ptosis => Loss of Muller’s muscle, only slight LPS intact 3. Anhidrosis In congenital/long-standing lesions, heterochromia will develop

Answer 540

Due to the interruption of the sympathetic chain in the level of the first, second or third order neurone: First order: => Brainstem disease – tumour, stroke, MS, syphilis Second order: => Intrathoracic lesions – Pancoast tumour, cervical rib, TB => Neck lesions – lymphadenopathy, trauma, thyroid surgery Third order: => ICA aneurysm => Migraine (transient) => Idiopathic

Answer 541

Pro-thrombotic risk factors: - Oral contraceptives - Pregnancy / puerperium - Malignancy - Genetic thrombophilia Head injury Recent LP Infection

Answer 542

Venous infarction leads to vascular congestion. Eventually there is haemorrhagic necrosis It can be split into cortical venous thrombosis and dural venous sinus thrombosis

Answer 543

Ocular pain, worse on movement Proptosis and chemosis Ophthalmoplegia Papilloedema Fever

Answer 544

Signs of raised ICP (headache, vomiting, fever, papilloedema, seizures).

Answer 545

CT – often normal LP – raised ICP CT/MRI venography may be required for diagnosis Suspect venous sinus thrombosis if there is thunderclap headache and raised ICP, with no signs of meningitis and no changes on CT.

Answer 546

= reactivation of varicella zoster infection within the dorsal root ganglia. Most commonly occurs in the lower thoracic dermatomes: - Pain and paraesthesia for several days - Erythema and a dermatomal eruption of vesicles - Increased burning and itching - Vesicles become pustular 2-3 days later and may separate 3 weeks later.

Answer 547

Infection of the 1st division of the 5th nerve. Can lead to uveitis, corneal scarring and secondary pan-ophthalmitis

Answer 548

VZV infection of the geniculate ganglion. Clinical features: - Facial palsy (often severe and irreversible) - Facial/ear pain - Vesicles in the ear canal, pinna and soft palate. May also be sensorineural deafness and vertigo and neuropathy of nerves 5, 9 & 10.

Answer 549

5-7 days oral acyclovir Paracetamol and amitriptyline for pain

Answer 550

Pain in previous shingles zone, occurring in 10% Burning, continuous pain Responds poorly to analgesia Amitriptyline is commonly used, plus topical capsaicin Associated with depression Gradual recovery over ~2 years

Answer 551

Presentation is dependent on the location of the tumour and its rate of growth: Signs/symptoms of raised ICP => Headache (morning/lying down), N&V, papilloedema Epileptic Seizures => Adults with an epileptic fit have a brain tumour until proven otherwise. Progressive neurological deterioration: - Increasing weakness - Sensory loss - Cranial nerve palsies - Dysphasia (if involving the dominant hemisphere)

Answer 552

These patients need urgent admission for investigation: - Early CT with contrast - MRI if no mass can be seen on CT

Answer 553

Dexamethasone 4-6mg QDS if any neurological deterioration/drowsiness Anticonvulsants – if presented with epilepsy Refer to neuro-oncology MDT => Neurosurgical intervention if accessible, often with adjunctive radiotherapy.

Answer 554

= a cluster of symptoms that occur in patients with cancer, that cannot be explained by the tumour/metastases or hormones normally secreted by the primary tissue from which the tumour arose. Seen in ~10% of patients with advanced malignant disease.

Answer 555

Myasthenia Gravis Lambert-Eaton Myasthenic syndrome Paraneoplastic sensory neuropathy Paraneoplastic cerebellar degeneration

Answer 556

=> Gives classic cerebellar signs – e.g. ataxic gait, dizziness, dysarthria => Frequently associated with Hodgkin’s Lymphoma, breast cancer, small cell lung cancer and ovarian cancer.

Answer 557

malignant glioma, meningioma, and astrocytoma

Answer 558

Most common adult primary malignancy, originating from astrocytes. Rapidly growing, thus present with signs of raised ICP Poor prognosis, with death often within 6 months of diagnosis

Answer 559

Generally benign, slow growing tumours arising from the meninges Surgical excision and debulking is undertaken wherever possible. Good prognosis following surgical excision.

Answer 560

Benign, slow-growing tumour that occur in young people. Can turn malignant in later life.

Answer 561

Originate from the ependymal cells lining the ventricles Most common in young people/children Usually malignant, but do not tend to recur after removal

Answer 562

Arise from the Schwann cells of the acoustic nerve More common in neurofibromatosis type II Presents with progressive unilateral sensorineural deafness, tinnitus, vertigo, facial nerve palsy. Tumour growth can cause cerebellar symptoms or bulbar palsy.

Answer 563

- Bronchus - Breast - Kidney - Colon - Thyroid - Malignant melanoma

Answer 564

= “simple faint” Due to sudden reflex bradycardia and peripheral vasodilation Occurs in response to standing, fear, venesection or pain. Patient is unconscious for less than 2 minutes. Recovery is rapid Treatment is not necessary

Answer 565

Vasovagal Postural hypotension Post-prandial hypotension Carotid sinus syncope (excessive vagal response – e.g. wearing tight collars). Anaemic syncope Micturition syncope (in men, due to parasympathetic overactivity). Coughing or exertion syncope.

Answer 566

Drop in SBP of 20mmHg or more on standing from a sitting/lying position. => Measure sitting, and then at 1, 2 and 3 minutes after standing up. Occurs due to blood pooling in the legs due to the influence of gravity

Answer 567

- Fluid depletion - Age-related autonomic dysfunction - Polypharmacy (vasodilating/diuretic drugs).

Answer 568

Drop in SBP of 20mmHg (or DBP of 10mmHg) after eating, due to pooling of blood in the splanchnic vasculature. Thought to be even more common than postural hypotension.

Answer 569

This is a clinical differentiation: => Witnessed jerking movements, incontinence, post-episode confusion and amnesia highly suggestive of a seizure. Cardiac evaluation can detect RFs for syncope (arrythmias, mechanical issues, etc.)

Answer 570

Advise patient against driving whilst undergoing investigation for the cause. Investigations: - Bloods – FBC, U&E, glucose - L/S BP or tilt table tests - ECG / 24-hour tape (heart block , arrythmias, long QT) - EEG/ sleep EEG - Echo - CT head

Answer 571

1. Muscular Dystrophies - Genetically determined diseases that result in progressive deterioration. 2. Myopathies: - Diverse group of conditions that are grouped due to their predominant effect on muscle. 3. Neurogenic disease: - Disease of peripheral nerves or motor neurones that cause secondary skeletal muscle atrophy.

Answer 572

Duchenne Muscular Dystrophy Becker Muscular Dystrophy Myotonic Dystrophy

Answer 573

Most common muscular dystrophy X-linked recessive, seen exclusively in males. => Can be spontaneous mutations Caused by a mutation in the dystrophin gene, making muscle fibres liable to break down with repeated contraction.

Answer 574

Onset in early childhood: - Global muscle weakness - Calf pseudohypertrophy – due to fatty replacement of muscle. - Gower’s sign – uses hands to climb up to standing. Prognosis is poor – patients usually die in late teens due to respiratory failure and cardiomyopathy

Answer 575

- Raised CK - Genetic testing / muscle biopsy can confirm Dx

Answer 576

Less common, producing partially functioning dystrophin As such, symptoms are milder and prognosis is better than Duchenne Patients generally survive until mid-40s.

Answer 577

Autosomal dominant condition, caused by a chloride channelopathy Shows “anticipation”, with symptoms more severe in each generation => Due to expansion of CTG repeat

Answer 578

Characterised by muscle weakness and myotonia => Inability to relax muscles Usually becomes apparent in adolescence, with facial and lower limb weakness. Also associated with non-muscular features: => Cataracts, frontal baldness, mental impairment, cardiac abnormalities.

Answer 579

Serum muscle enzymes – Creatine Kinase => Raised in muscular dystrophies and inflammatory muscle disorders => Normal in MG Electromyography: => Classical trace for myopathy, denervation, myotonic discharges and in MG. Muscle biopsy: => Can differentiate between denervation and muscular disease.

Answer 580

manage as per the REPAIR mnemonic. Spasticity: - Physical Mx => PT, gait retraining, removal of exacerbating stimuli (e.g. constipation, UTI, pressure ulcers). - Surgical Mx: => Tendon lengthening, releases for fixed deformities, electrostimulation therapy. - Medical Mx: => Baclofen, dantrolene, benzodiazepines, botox injections. Contractures: - Aim to prevent development with good management of spasticity - If contractures are present, orthopaedic referral may be appropriate. - PT and aids are also appropriate.

Answer 581

Drugs/dehydration => Drugs – withdrawal/new/toxicity => including opiates, antihistamines, BZDs, antipsychotics, antimuscarinics, alcohol. Electrolyte imbalance Level of pain Infection/inflammation Respiratory failure / Reduced sensory input Impaction of faeces / Intracranial Urinary retention Metabolic / MI

Answer 582

Symptoms depend on the type. HYPERACTIVE: * Abnormally alert, Agitation/restlessness, disorientation, hallucinations, aggression, wandering, inappropriate behaviour. * Tx – delirium pathway HYPOACTIVE: * More common * Often unrecognised (so increased mortality), presents similar to depression. * Withdrawn, not eating/drinking, drowsy, disorganised. Can also have a mixed delirium.

Answer 583

Collateral Hx (establish baseline cognition). Physical examination (conscious level, infection, neurology). Confusion Bloods => FBC, CRP, U&Es, LFTs, TFTs, glucose, Ca, B12, folate Urinalysis CXR, ECG, CT/MRI Assess nutritional status Medication review

Answer 584

Treat the underlying cause (if ignored => high mortality). Reduce medications – avoid opiates, anticholinergics. Reassure and keep orientated, active, hydrated, nourished. Optimise senses and promote good sleep hygiene. Only use drugs if other interventions have failed and patient is a risk to themselves or others. - Haloperidol 0.5mg = 1st line - Lorazepam 0.5mg (if haloperidol is contraindicated – Parkinson’s, LB dementia). - Only use short-term (usually 1 week or less).

Answer 585

1. Tremor 2. Rigidity 3. Bradykinesia

Answer 586

4 – 7 Hz Characteristic “pill-rolling” movement between thumb and finger Occurs at rest Decreases with action (e.g. on finger-to-nose test) Increases with anxiety/anger/excitement Positive glabellar tap sign (tap smooth part of the forehead above the nose and between the eyebrows) => Leads to excessive blinking

Answer 587

Increased tone throughout the range of limb movement It is equal in opposing muscle groups, giving “lead pipe” rigidity Patient may have problems getting up from a chair

Answer 588

Difficulty initiating movement Progressive reduction in speed/amplitude of repetitive actions Spontaneous blinking rate is reduced. Facial immobility gives mask-like face => hypomimia. Combined with hypersalivation => drooling

Answer 589

Idiopathic = Parkinson’s disease Drug-induced: => Neuroleptics, prochlorperazine, metoclopramide, TCAs, methyldopa Vascular: => Multiple cerebral infarcts Toxin induced => Wilson’s disease Post-encephalopathy Parkinson’s-plus Syndromes

Answer 590

= Rare alternative causes that should be screened for before diagnosing with Parkinson’s disease. - Progressive Supranuclear Palsy - Multiple system atrophy - Lewy Body Dementia - Vascular Parkinsonism - Cortico-basal degeneration

Answer 591

- Symmetrical onset, tremor is unusual - Early postural instability (falls) - Dementia develops early - Vertical gaze palsy ( = limitation of movement in down gaze)

Answer 592

Early autonomic features * Postural hypotension, bladder dysfunction, excess sweating Cerebellar signs also present * Nystagmus in horizontal gaze Pyramidal (UMN) signs present * Extensor plantars, hyperreflexia

Answer 593

Early dementia, with fluctuating cognition and visual hallucinations. Symmetrical motor signs

Answer 594

Strokes affecting basal ganglia Symptoms worse in legs than arms Pyramidal signs present

Answer 595

Akinetic rigidity involving one limb Cortical sensory loss – e.g. asterognosis

Answer 596

= A neurodegenerative disorder Caused by a loss of the dopamine producing cells in the Substantia Nigra. The results in REDUCED DOPAMINE ACTIVITY within the corpus striatum of the basal ganglia, leading to Parkinsonism. 60% of nigrostriatal neurones have to be lost before symptoms appear. => Surviving neurones increase dopamine production => Target striatal neurones increase receptor number.

Answer 597

Onset is typically asymmetrical and there is persistent asymmetry in the severity of the classical triad of Parkinsonism. Motor and Non-motor symptoms

Answer 598

* Bradykinesia * Rigidity * Postural instability * Resting tremor * Freezing => Narrow/confined spaces => Changing direction * Dystonia (painful cramping in feet/legs) - worse at night * Dysphagia * “Classic Parkinson’s Gait” – shuffling/small steps, stooped over, reduced arm swings.

Answer 599

* Masked face * Hypophonia (deep, soft, monotonous voice) * Micrographia (progressively smaller handwriting) * Depression/anxiety * Psychosis * Anosmia * Insomnia/REM sleep disorder/restless legs * Fatigue * Constipation/urinary incontinence * Seborrhoeic dermatitis * Cognitive impairment

Answer 600

Diagnosis is clinical, after ruling out other causes of Parkinsonism.

Answer 601

There is no cure. Care should be under a specialist MDT, including a Parkinson’s nurse. 1. Levodopa Monotherapy 2. Dopamine Receptor Agonists 3. Levodopa Dual Therapy – Dopamine Metabolism inhibitor 4. Non-pharmacological - Patient education – advice to minimise “freezing” - Comprehensive Geriatric Assessment - Social support - Physio/OT 5. Treatment of Non-motor Symptoms - Constipation – dietary fibre, water, mild osmotic laxatives. - Urinary incontinence – timed voids, bladder antispasmodics. - Sleep – make sleeping environment safer. - Orthostatic hypotension – reduce/stop antihypertensives or diuretics, possibly fludrocortisone/midodrine.

Answer 602

A dopamine precursor (dopamine itself cannot cross the BBB). Acts to increase synaptic dopamine. Combined with carbidopa to prevent peripheral metabolism to dopamine (but cannot cross the BBB so allows action of L-dopa in the CNS). Usual maximum dose 600-1000mg / day Complications may arise after 4-6 years and efficacy reduces (narrowed therapeutic window). SEs – dyskinesia (uncontrollable wriggling), confusion, depression, insomnia.

Answer 603

e.g. Ropinirole, Rotigotine (patch), bromocriptine Activates post-synaptic receptors. Can be used as monotherapy in early disease to delay the use of L-dopa, or can be used as an adjunct to L-dopa. Generally less effective, but cause fewer unwanted dyskinesias. SEs – confusion, hallucinations, impulsive control disorder (gambling, hypersexuality).

Answer 604

[1] Dopamine Metabolism inhibitors: MAO-B inhibitors (selegiline/rasagiline) * Can increase duration of response to L-dopa. * SE – postural hypotension [2] COMT inhibitors (entacapone) * Block L-dopa metabolism * SEs – sleepiness, hallucinations, impulsiveness. [3] Amantadine – useful if prominent dyskinesias.

Answer 605

= Process affecting nerve roots

Answer 606

= Pathological process affecting a peripheral nerve(s)

Answer 607

= Process affecting a single nerve

Answer 608

= Process affecting a single nerve

Answer 609

= Process affecting several individual nerves

Answer 610

Diffuse, symmetrical disease, usually beginning peripherally. Can be motor/sensory/autonomic or combinations of these Can be broadly classified into demyelinating or axonal types. Widespread loss of tendon reflexes is usual, as well as “glove and stocking” sensory loss.

Answer 611

Amiodarone, statins, hydralazine, phenytoin, ABX

Answer 612

DM, Carcinomatous neuropathy (myeloma/paraneoplastic syndrome) B-vitamin deficiency Drugs.

Answer 613

Can be separated by nerve conduction studies DEMYELINATING: - Damage spares axons, but affects Schwann cells, more common in immune-mediated disease such as GBS - Inferred by decreased conduction velocity - Schwann cells can regrow, so will improve with Tx AXONAL: - Nerve cell bodies are unable to maintain long axonal processes, leading to degeneration that starts at the periphery, progressing upwards to the neuronal cell. - Inferred by reduced amplitude of nerve impulses - Axons cannot regrow, thus treatment outcomes are poor.

Answer 614

Providing the cell bodies are intact, the nerves are able to regenerate at a rate of up to 1mm per day.

Answer 615

Bloods: - FBC, U&E, LFTs, HbA1c, B12/folate - ANCA, VDRL (syphilis), autoantibodies Nerve conduction studies => Demyelinating or axonal? LP: => Raised protein in GBS / CIDP Peripheral nerve biopsy if diagnosis uncertain.

Answer 616

Diagnosis involves: 1) ruling out other causes of hepatomegaly (such as alcoholism, viral hepatitis, and auto-immune liver disease) 2) evidence of of hepatic steatosis (liver biopsy or radiology)

Answer 617

urinary tract infection menstruation vigorous exercise (this normally settles after around 3 days) sexual intercourse

Answer 618

cancer (bladder, renal, prostate) stones benign prostatic hyperplasia prostatitis urethritis e.g. Chlamydia renal causes: IgA nephropathy, thin basement membrane disease

Answer 619

low T3/T4 levels alongside an inappropriately normal TSH in the context of an acutely unwell patient Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.

Answer 620

- Anaemia (iron deficient) - Loss of weight - Anorexia - Recent onset, progressive symptoms - Melaena or haematemesis - Swallowing difficulties. - >55 years of age

Answer 621

AGRANULOCYTOSIS - Advise (including in writing) to see their GP immediately if they develop any signs of mouth ulceration, sore throat or fever.

Medicine 2 Flashcards

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