Flashcards in C 1.11 MANAGEMENT OF ADULTS AND CHILDREN AS IN-PATIENTS, INCLUDING THE MEDICALLY AT-RISK PATIENT Deck (27):
Cardinal features of inflammation
Altered function (functiolaesa)
Immune system made up of:
cells - immunocytes, various different types
All designed to identify and destroy pathogens
Organs of the immune system
Primary organs :lymphoid:
- Bone marrow
- lymph vessels
- lymph nodes
Programmed cell death
Bone marrow-derived white blood cells
- Myeloid leukocytes
- Lymphoid leukocytes
Macrophages and polymorphonuclear leukocytes -
Phagocytic - non-specifically ingest and destroy microbes
recognise foreign proteins (antigens)
Differentiated B-lymphocytes (plasma cells) secrete antibodies (immunoglobulins) that specifically bind to and eliminated pathogens
Bind to antigens presented on the surface of antigen presenting cells (langerhans, macrophages, dendritic cells) and eliminated intracellular pathogens (eg viruses) out of reach of antibiodies.
T-cytotoxic lymphocytes (that express CD8 surface receptor) destroy damaged cells including virally infected and cancer cells.
T-helper cells express the CD4 cell surface receptor, producing a wide range of cytokines that enhance other immune cells function
Natural Killer Cells
NK lymphocytes produce cytokines and cause direct lysis of infected or damaged cells
Characterised by variable shapes of their nuclei and presence of granules in their cytoplasm. Granules contain immune mediators.
Immune proteins - Cytokines
heterogenous group of small proteins, signalling molecules used in lots of biological functions including inflammation, differentiation, activation, proliferation, apoptosis.
Include interleukins (ILs), interferons (IFNs), Tumour necrosis factor (TNF), Cehmokines, and colony stimulating factors (CSFs)
Immune proteins - Complement proteins
Activated as a proteolytic cascade - coat surface of pathogens, stimulating their lysis or phagocytosis by immune cells.
Complement activation precepitates inflammation: recruiting blood and immune cells to the area
Sickle cell anaemia
Normal Hb is HbA, Defective sickle haemaglobin - HbS
Sickle cell disease - Autosomal recessive inheritance 2 HbS genes (HbSS)
Sickle cell Trait - HbSA - innocuous - usually asymptomatic and rarely anaemia or other complications, unless exposed to extreme hypoxia (e.g. v poor anaesthesia)
Trait confers relative immunity against the malaria parasite during childhood in the critical period between the decline of the passively acquired maternal immunity and the development of the actively acquired immunity.
25% of African population carry HbS gene, also affects people of Middle East and Mediterranean origin.
Hb in RBCs - 4 components 2 beta chains and 2 alpha chains. In fetal Hb 2 alpha chains and 2 others
HbS molecules form due to substitution of valine for glutamic acid in the beta chain of Hb leading to increased rigidity of red cells and classic sickle appearance. This results in haemolysis and vaso-occlusion, leading to tissue infarction. Precipitated by deoxygenation (i.e. when in low flow vessels) or acidosis...
Haemolysis causes: (severity varies)
- anaemia (generally 6-8g/dL) although tends to be asymtomatic due to hyperdynamic circulation (increased circulatory volume) and lower oxygen affinity of HbS, so oxygen released to the tissues more readily then HbA
- high reticulocyte count (precursor to RBCs)
Fall in Hb can be due to
- Aplastic crisis - viral infection destroying erythrocyte precursors
- Acute sequestration crisis - liver and spleen engorged
- haemolysis due to drugs or infection
- causes avascular necrosis of bone marrow - bone pain crises, precipitated by hyposia, dehydration or infection
- splenic atrophy (increased susceptibility to infection - pneumococcus, salmonella and haemophilus)
- cerebral infarction (fits and hemiplegia
- retinal ischaemia - proliferative sickle retinopathy and visual loss
Acute chest syndrome most common cause of death - medical emergency - fever, cough, dyspnoea, pulmonary infiltrates on CXR. Caused by infection, fat embolism (from necrotic bone marrow),
Prognosis - median survival 40-50 years
Mainstays of treatment - oxygen, fluids, antibiotics, opioid analgesics, transfusions
Emotional stress can also play a part in precipitation of crises.
Dental management of Sickle Cell Disease
Routine treatment in non-crisis period only.
During crisis period - only treatment to manage pain and infection.
Preventative regime important - appropriate use of fluoride tooth pastes and fissure sealants.
Treatment should be planned for early in the morning, and kept as breif and stress free as possible.
Prophylactic antibiotics - pre-op co-amoxiclav or doxycycline and metronidazole deemed appropriate in patients undergoing oral surgery procedures, although little evidence to support this. Patients likely to be on low dose prophylaxis of antibiotics already.
Analgesia - paracetamol and codine recommended as NSAIDs and aspirin may contribute to acidosis which can precipitate crises, and patients may have altered renal function due to vascular damage to the kidneys.
LA with vasoconstrictor not contraindicated (although theoretically contribute to hypoxia and vascular stasis)
GA - hazardous - avoid wherever possible - change in oxygen PP, blood flow, pH and lowered temperature which accompany the anaesthetic may promote intravascular sickling and hence a painful, vaso-occlusive crisis. This needs to be considered and 5 mins of pre-op oxygen is advocated prior to anaesthesia.
IHS good for anxious patients as O2 delivered throughout, so no hypoxia risk
If very anxious then the risk of crisis precipitation due to stress may outweigh the risks of IVS - mainly risk of respiratory depression. ASA III - not in primary care, but by experienced sedationist. Give pre-IVS oxygenation 2-4L/min by nasal cannula for 5 mins, throughout procedure and recovery.for IHS pre-oxygenate, and post-operative oxygen should be given for 5mins after Nitrous oxide administration ceases.
Warfarin: Vit K
Organophosphate weedkiller: Atropine
Salicylates: Activated Charcoal, Urine Alkalinisation
Theophylline: Activated charcoal
Anaemia - haematological pathology findings
- Normal range (g/dL) F - 11.5-15.5, M - 13-18
- normal range (10_12/L) F:3.9-5.1, M:4.5-6
Low haematocrit (L/L) (Packed cell volume)
- normal range F:0.36-0.45, M: 0.42-0.53
If anaemic due to increase in plasma volume (massive splenomegaly, or use of fluids in hypovolaemic shock for example - dilutional anaemia, with only low Hb, but other ranges normal.
Anaemia - Clinical features
If slow onset - compensation and therefore fewer symptoms
Symptoms non-specific - fatigue, faintness, breathlessness.
If co-existing atheromatous vascular disease - angina, claudication
Pale skin and mucous membranes
Possibly tachycardia, systolic flow murmur.
Cardiac failure may occur in elderly or those with compromised cardiac function.
Decreased Hb within RBCs
MCV less than 80fL
Decreased MCH (mean corpuscular haemoglobin)
Decreased MCHC (mean corpuscular haemoglobin concentration)
Hypochromic appearance on blood film
- Iron Deficiency
- Anaemia of Chronic Disease
- Sideroblastic Anaemia (rare disorder of haem syntheseis)
Iron Deficiency Anaemia
A cause of Microcytic Hypochromic Anaemia
Causes of iron deficiency anaemia
- menstural bleeding - premenopausal women
- pregnancy [increased demand]
- decreased absorption in small bowel
- poor iron intake
- chronic occult GI blood loss (men, post-menopausal women)
Additional clinical features:
- brittle hair and nails
- atrophic glossitis
- angular stomatitis
- koilonychia (spoon shaped nails)
- rarely pharengeal webs which may cause dysphasia [paterson-brown-kelly syndrome]
Additional findings on haematinic investigation
- low Hb with low MCV
- low ferritin
- low serum iron
Management - Treat underlying cause, oral iron, parental iron only if patients intolerant to oral iron or malabsorption
Anaemia of Chronic Disease
- normocytic or microcytic anaemia
Variety of chronic diseases
- chronic renal failure, inflammatory diseases such as chron's, chronic infections (e.g. TB, IE),
- Presents as a normochromic, normocytic or microcytic anaemia
- low serum iron
- increased or normal ferritin
- results from the decreased release of iron from bone marrow to developing eyrthroblasts, inadequate erythropoietin response to the anaemia, decreased red cell survival
- treatment - of underlying cause
- megaloblastic and non-megaloblastic types
Megaloblastic Macrocytic Anaemia
- delayed RBC maturation due to defective DNA synthesis in the bone marrow
- may also affect the white cells (causing leukopenia) and platelets (causing thrombocytopenia)
- most common cause - B12 deficiency or folate (both required for DNA synthesis)
Non-megaloblastic Macrocytic Anaemia
- ? lipid accumulation in RBCs
- most common cause in UK - alcohol excess
- pregnancy, newborn
- liver disease, hypothyroidism, haematological disorders, MDS (mylodyplastic syndrome) & others
Causes of B12 deficiency
- Low dietary intake (vegans)
- Stomach - pernicious anaemia, gastrectomy
- Small bowel - ileal disease or resection, coeliac disease, tropical sprue, bacterial overgrowth
Pernicious anaemia (most common cause of B12 deficiency western world)
- Autoimmune condition with atrophy of gastric mucosa and failure of intrinsic factor production causing failure of B12 absorption
- elderly people - particularly women and people with fair har and blue eyes. Associated with other autoimmune diseases
Symptoms - glossitis, angular stomatitis, mild jaundice. If servere - neurological features including polyneuropathy, weakness, ataxia
Treatment - B12 injections twice weekly for 3 weeks, then 3/12 injections to maintain levels
- found in green veg and offal, absorbed in upper GI
- poor intake: alcoholic, anorexia, poverty, old age
- excessive utilisation: pregnancy, lactation, chronic haemolytic anaemia, malignant and inflammatory disease, dialysis
- drugs: phenytoin, trimethoprim, sulfasalazine
Treatment: oral folic acid (higher doses in malabsorption)
Given prophylactically to pregnant women and before conception and first 3/12 of pregnancy to reduce the risk of neural tube defects (spina bifida etc)
Aplastic Anaemia - caused by marrow failure
- deficiency of all cell elements of the blood with hypocellularity (aplasia) of bone marrow. Uncommon but serious
- causes: congenical, aquired, chemicals, drugs (cytotoxics, chloramphenicol, gold), radiation, infections (hepatitis, HIV, sepsis)
- clinical features - anaemia, increased susceptibility to infection, bleeding
- Bloods - pancytopenia with low/absent reticulocytes. Bone marrow - hypocellular with increased fat spaces
- differentiate from other causes of pancytopenia -eg lymphoma (in bone marrow), acute leukaemia, myeloma, secondary carcinoma, myelofibrosis, MDS, SLE, hyperspenism
Treatment - of cause
supportive care -transfusions, antibiotic therapy as necessary
- increased destruction of red cells with reduction of circulating life span (normally 120 days)
- inherited - includes thalassemia, sickle cell disease, G6PD deficiency
- acquired - includes spenomegaly, drugs, chemicals, infections, (e.g. malaria)
- reduced production of one or more of the globin chains in haemoglobin in RBCs (alpha or beta) resulting in death of RBC precursors (ineffective erythropoiesis)
- 2 types - alpha and beta (relates to which chain has reduction in synthesis)
- beta trait - asymptomatic heterozygous. Anaemia mild or absent, low MCV and MCH. Iron stores and ferritin normal
- beta thalassaemia intermedia - moderate anaemia, splenomegaly, bone deformities, gallstones
- beta thalassaemia major - severe anaemia in first year of life, failure to thrive and recurrent infections. bony abnormalities, enlarged maxilla and prominent frontal and parietal bones. Resumption of haemopoiesis in spleen and liver (extramedullary) - leads to hepatosplenomegaly
Treatment - blood transfusions to keep Hb>10
Complications - iron overload - damage to endocrine glands, liver pancreas and heart
BMT has been used