León III: coronación imperial
DESTRUCCIÓN DEL IMPERIO CARLOVINGIO (814-887) I.—Luis el Bondadoso 1 y los primeros repartos
1. Persistent tiredness or fatigueability that persists or relapses for >6 months 2. >4 of the following symptoms persistent for >6 months:
o ↓memory, concentration o Tender cervical/ axillary lymph
nodes
o Multi-joint pain o Sore throat o Muscle pain
o New headaches o Unrefreshing sleep
Clinical Approach
History
• Onset, duration, relation to other symptoms
• Attributions – what the patient thinks is the cause, how it is affecting them
• Physical features – general health, diet, appetite, systems review
• Recent infection e.g. glandular fever
• Medications
• Substance use – alcohol, marijuana, other illicit drugs
• Depression/anxiety history
• Sleep – quality, snoring, apnoea
• Social history – relationships, work, stress, last holiday
• Sexual history + HIV, Hep C
• Occupational exposure – heavy metals, CO Examination
• Lymphadenopathy
• Cardiovascular signs
• Full mental state examination
Investigation
Tired all the time (TATT) screen
• Full blood count
• Erythrocyte sedimentation rate
• Urea, electrolyes, creatinine
• Urine culture and microscopy
• HIV, hepatitis B and C
• Liver function tests
• Iron studies – serum iron and Ferritin
• Thyroid stimulating hormone
• Glucose
Fever
• Normal body temperature: 36.8 ±0.4°C at ~6am and is higher between 4-6pm
• Fever: >37.2°C (at 6am, or 37.7°C at 4pm)
Pathogenesis
• ↑ hypothalamic set point → ↑body temp. until affector neurons register blood temp. at new set point Mechanism
1. Pyrogens → release of prostaglandin E2 (PGE2) by hypothalamic endothelial cells 2. ↑PGE2 → release of cAMP by glial cells in the hypothalamus
o PGE2 release in peripheral cells → muscle and joint pain 3. ↑cAMP → ↑ set point by neuronal cells in the thermoregulatory centre
Aetiology
1. Infections – viral bacterial, malaria, syphilis etc.
2. Malignancy – lymphoma, carcinoma
3. Rheumatological disorder – SLE, sarcoid, rheumatoid arthritis 4. Drug fever – reaction with medicine (usually accompanied by rash) 5. Pulmonary embolism (mild fever)
6. Osteomyelitis Endogenous Pyrogens IL-1, IL-6, TNF-α, IFN- α
Exogenous Pyrogens Bacteria, endotoxins, hormones, medications
↑PGE2 ↑cAMP
Muscle/joint pain Vasoconstriction
Shivering
↑ Liver metabolism
↑ Set point ↑"Temperature
Hypothalamus
Lymphadenopathy
Aetiology
1. Infection
o Bacterial – all pyogenic bacteria, syphilis o Mycobacterial – tuberculosis, leprosy o Fungal – histoplasmosis
o Chlamydial
o Parasitic – toxoplasmosis, trypanosomiasis, filariasis
o Viral – Epstein-Barr virus, cytomegalovirus, rubella, hepatitis, HIV 2. Benign immune disorder
o Autoimmine - rheumatoid arthritis, systemic lupus erythematosus o Serum sickness
o Drug reactions (e.g. to phenytoin) o Langerhans cell histiocytosis 3. Malignant immune disorder
o Leukaemia – acute/chronic, myeloid/lymphoid o Lymphoma – Hodgkin’s, non-Hodgkin’s
o Monoclonal gammopathy - multiple myeloma, Waldenström’s macroglobulinaemia o Malignant histiocytosis
4. Other malignancies – breast, lung, melanoma, head & neck, GIT, germ cell 5. Lipid storage diseases – Gaucher’s disease, Niemann-Pick disease 6. Endocrinopathies
o Thyroid disease - hyperthyroidism; thyroiditis o Andrenal insufficiency
7. Miscellaneous o Sarcoidosis o Amyloidosis
o Dermatopathic lymphadenitis
History
• Age, sex, occupation
o Children – usually benign e.g. viral, bacterial, toxoplasmosis o > age 50 – incidence of malignant disorders increases significantly
• Localised symptoms – suggests infection or malignancy
• Exposure – cats, undercooked meat, travel, unsafe sexual or drug activity
• Indicators of systemic involvement -suggest tuberculosis, lymphoma or other malignancy o Fever
o Night sweats
o Unexpected weight loss of >10%
• Medications – e.g. phenytoin
• Generalised pruritis
• Pain – from inflammation
Examination
1. Location – localised or generalised 2. Size
o <1cm →$benign o 1+2.25$cm$→$8%$malignant o >2.25$cm$→$38%$malignant 3. Consistency
o Hard – malignant leading to fibrosis
o Firm/rubbery – lymphoma or chronic lymphocytic lymphoma 4. Fixation - chronic infection or malignancy
5. Tenderness – due to inflammation
o Infection → rapid growth within capsule → tenderness
o Malignancy → gradual expansion of entire encapsulated node → no tenderness 6. Signs of inflammation over the node
7. Splenomegaly – systemic illness e.g. infectious mononucleosis, lymphoma, leukaemia, SLE, sarcoidosis
Investigations
1. Observe for 3-4 weeks if there are no clues about aetiology 2. Full blood count
3. Serology – EBV, CMV, toxoplasmosis, HIV, Bartonella henselae, syphilis, TB 4. Chest X-ray
5. Biopsy
Types of Biopsy
1. Excision biopsy – for when malignancy is suspected and the patient has no history of malignancy
2. Core biopsy – for when lymphoma is suspected and lymph nodes are not easily obtainable
3. Fine needle aspirate (FNA) – to confirm recurrence of malignancy, but not for diagnosis
Who to Biopsy
• Patients >40 years
• > 2cm in size
• Abnormal chest X-ray
• Supraclavicular LN involvement
• Hard consistency
• Generalised pruritis
• No symptoms of local/systemic infection
Bleeding
• Purpura: bleeding into the skin or mucous membranes o Petechiae: smaller purpuric lesions ≤2mm o Ecchymoses: purpuric lesions >2mm
Aetiology
Vessel Wall Abnormalities
Platelet count, bleeding time, PT and aPTT are usually normal
1. Infections: meningococcaemia, septicaemia, infective endocarditis, rickets o Microbial damage to microvasculature, or DIC
2. Drug Reactions: usually vascular injury is mediated by deposition of drug-induced immune complexes 3. Scurvy & Ehlers-Danlos Syndrome: microvascular bleeding resulting from defects in collagen
Platelet Deficiency
Thrombocytopenia: reduced platelet number - <100,000 platelets/μL 1. Decreased production
o Depression of bone marrow – aplastic anaemia, leukaemia
o Selective depression of megakaryocytes – drugs, alcohol, measles, HIV, myelodysplastic syndromes 2. Decreased survival
o Immunological platelet destruction – autoimmune, alloimmune (post-transfusion), drugs, infection o Non-immunological destruction – DIC, mechanical injury
3. Sequestration – splenomegaly 4. Dilution – massive transfusions
Defective Platelet Function
1. Defective adhesion to subendothelial matrix – e.g. Bernard-Soulier syndrome (defect in vWF receptor) 2. Defective aggregation – e.g. Glanzmann thrombasthenia
3. Disorders of platelet secretion – defective release of factors e.g. TXA2, ADP – e.g. aspirin intake
Abnormalities in Clotting Factors
1. Hereditary deficiencies typically affect a single clotting factor o Haemophilia A – factor VIII
o Haemophilia B – factor IX o Von Willebrand disease – vW factor
2. Acquired deficiencies usually involve multiple coagulation factors o Vitamin K deficiency →$↓ factors, II, VII, IX, X, protein C
Most Probable Most Serious
Assessment
History Trauma
General health – tiredness, weight loss, fever, night sweats Medications
o Steroids o Cytotoxic drugs o Gold
o Heparin o Phenylbutazone o Sulphonamides
o Quinine o Thiazide diuretics o Chlorampenicol
o Aspirin o NSAIDS o Warfarin Family history
o Sex-linked recessive – haemophilia A/B
o Autosomal dominant – von Willebrand disease, dysfibrinogenaemias o Autosomal recessive – coagulation facor V, VII, X deficiency
Factors suggesting a bleeding defect – spontaneous haemorrhage, sever/recurrent bleeding episodes, bleeding from multiple sites, bleeding out of proportion to trauma
o Early bleeding following trauma → platelet deficiency
o Delayed bleeding after initial homeostasis → coagulation factor deficiency
o Normal history of previous coagulative stresses → acquired problem → drugs, malignancy, liver
Examination
Nature of bleeding and rash distribution
o Senile purpura – dorsum of hands, extensor surface of forearms and shins Lips and oral mucosa – telangiectasia, gum hypertrophy
Signs of malignancy – sternal tenderness, lymphadenopathy, splenomegaly Urinalysis
Investigations
Tests Method Normal Abnormal Result
Bleeding Time Platelets An automated cut with a BP
cuff set to 40mmHg 2-8 min Von Willebrand disease, ↓platelets, added to a plasma sample,
coagulation time is measured 12-15 sec ↓ vitamin K, DIC, GIT malabsorption,
Contact activation by phospholipid, Ca2+ added,
coagulation time is measured 25-39 sec Heparin, haemophilia
Thrombin Time Common pathway
An excess of thrombin is added to a plasma sample,
coagulation time is measured 12-18 sec ↓ vitamin K, warfarin