GP Flashcards
Define Asthma
Chronic cough, dyspnoea and wheeze, characterised by reversible airway obstruction, airway hypersensitivity and inflamed bronchioles
This can be allergic/IgE mediated, or non IgE mediated (exercise, cold air and stress)
Pathophysiology of asthma
Allergen picked up by dendritic cells and presented to Th2 cells, which respond by releasing cytokines, releasing IgE which bind to mast cells, causing mast cell degranulation. This releases histamine, leukotrienes, prostaglandin.
This causes chronic airway inflammation causing:
- Bronchoconstriction and smooth muscle spasm
- Mucus hypersecretion
Common triggers of asthma
- Pollen, dust mites, grass
- Cold air
- Exercise
- Pets
- Tobacco smoke
- Occupational allergens (bakers, manufacturers, lab work, welding)
- Household mould
Signs/symptoms of asthma
Episodic shortness of breath, usually after trigger exposure.
- Diurnal PEFR variation (worse at night/early morning)
- Usually dry cough
- Expiratory wheezing/dyspnoea
- Chest tightness
Asthma patient mucus microscopy result
Will contain spiral mucus plugs - casts from small bronchioles
Investigations in Asthma
Spirometry:
-FEV1/FVC <80% (obstructive picture)
- Bronchdilator reversibility
FeNO (Fraction of exhaled Nitric Oxide) - 40ppb in adults, 35 in kids. (parts per billion)
GOLD: PEFR - measure multiple times a day for 2-4 weeks. >20% variability diagnostic
Patient taking regular aspirin/NSAIDs comes in with asthma-esque symptoms. What is this suggestive of?
Samter’s triad
What is Samter’s triad
Inflammation and swelling of the airways in response to aspirin or NSAIDs
Leads to:
- Chronic asthma-esque history
- Recurrent nasal polyps
- Aspirin intolerance
Asthma management algorithm
1) SABA (Salbutamol)
2) SABA + lowdose ICS (beclometasone)
3) SABA + lowdose ICS + LTRA (montelukast)
4) SABA + lowdose ICS + LABA (Salmeterol) + LTRA in adults, - LTRA in kids.
What are the goals of stepwise management in asthma
- Aim to use the lowest effective doses possible, only stepping up if previous treatment ineffective
- Step down treatment every 3 months and reasess
- Annual asthma reviews for stable asthma
Give the PEFR, speech, resp and cardio ranges of moderate, severe and life threatening asthma exacerbations
PEFR
- M - 50-75% of best/predicted
- S - 33-50%
- LT - <33%
Speech
- M - normal
- S - cant complete sentences
- LT - Silent, exhausted, confused, coma
Resp
- M - RR<25/min
- S - RR>25/min
- LT - O2 sats <92%, chest silent, reduced respiratory effort or cyanosis
Cardio
- M - Pulse <110
- S - Pulse >110
- LT - Bradycardia, dysrhythmia, hypotension
Signs of acute asthma exacerbation
- Progressively worsening dyspnoea
- Accessory muscle usage
- Tachypnoea
- Cyanosis
- Silent chest
Define bronchodilator reversibility
> 12% increase in FEV1, and >200ml increase in FVC
Management of acute asthma attack
Hospital if life threatening or near-fatal asthma attack (High pCO2/need for ventilation), or if bronchodilator irreversible.
- Salbutamol up to 10mg/hour (1 puff every 30-60 seconds up to 10 puffs)
- Ipratropium bromide (SAMA)
- 3-5 days oral prednisolone for ALL kids with exacerbation
- MgSO4 if PEFR <50% and no bronchodilator response
Checks to do at annual asthma review
- Inhaler technique
- Symptom scoring
- Check HPC
- Review treatment
- Check growth in children, and potentially do spirometry
Extrinsic pathway of coagulation cascade
3,7,10
endothelial damage = 3 (tissue factor) -> 3a.
3a = 7 -> 7a
7a + calcium -> activate 10 to 10a
Intrinsic pathway of coagulation cascade
12,11,9,8,10
Collagen exposure causes activation of 12 -> 12a
12a = 11 -> 11a
11a activates 8 and 9 to 8a and 9a.
8a and 9a activate 10 to 10a.
Common pathway of coagulation cascade
10a and 5a and calcium -> 2 to 2a (thrombin).
2a activates 1 (fibrinogen) to 1a (fibrin)
2a activates Stabilising factor (13) to 13a, which forms stable clot with 1a and calcium.
What is PT, and how is this used to calculate INR. Reasons INR may be raised
Prothrombin time - Coagulation speed through extrinsic pathway (3,7,10)
INR = (patient’s PT/reference PT)
Vit K deficiency, Anticoags, liver disease, disseminated intravascular coagulation
What is APTT and what conditions affect this BUT NOT PT
Activated Partial Thromboplastin Time
Coagulation speed through intrinsic pathway
Affected by:
haemophilia A, B and Von Willebrand Disease
What is acute bronchitis
Self limiting chest infection. Assoicated with oedematous large airways and sputum productions, may cause wheeze but no other focal chest signs (crackles, dullness to percussion, bronchial breathing etc).
How does bronchitis present
Cough
Sore throat
Rhinorrhoea
Wheeze (not always present)
Investigations and management in bronchitis
Clinical diagnosis
Analgesia, fluid intake.
Only do antibiotics if:
- Systemically very unwell
- Pre-existing comorbidities
- CRP 20-100
What is allergic rhinitis
IgE mediated T1 hypersensitivity reaction. Environmental allergens cause allergic inflammatory response in nasal mucosa.
Can be:
- Seasonal (hay fever)
- Perennial (year round - dust etc)
- Occupational (school/work etc)
Nasal spray technique
Left hand when spraying into right nostril. Slightly outwards, away from nasal septum. Do not sniff, shouldnt taste in back of throat
General anaemia signs
Pale skin
Conjunctival pallor
Bounding pulse/tachycardia
Dizziness
Fatigue
Postural hypotension
General anaemia symptoms
Tiredness, short of breath, headaches, palpitations, dizziness, syncope
Causes of microcytic anaemia
TAILS
T - Thalassaemia!
A - Anaemia of chronic disease
I - Iron deficiency anaemia!
L - Lead poisoning
S- Sideroblastic anaemia!
Causes of normocytic anaemia
Can be haemolytic or non haemolytic.
AAAH
A - Acute blood loss
A - Anaemia of chronic disease
A - Aplastic anaemia
H - Haemolytic anaemias (other card)
Normocytic haemolytic causes of anaemia (5)
Normocytic
Sickle cell
G6PD
AHA
Hereditary spheryocytosis
Malaria
Causes of macrocytic anaemia
Can be Megaloblastic (large RBC) or normoblastic.
Megaloblastic - Due vitamin deficiency leading to impaired DNA synthesis preventing cells from dividing normally.
- B12 deficiency
- Folate deficiency
- Secondary to methotrexate
Normoblastic -
- Alcohol
- Hypothyroidism
- Liver disease
- Drugs such as azathioprine
- Pregnancy
How is iron normally stored and made available?
- Iron exists bound to haem/myoglobin (Fe2+) or unbound (Fe3+)
- Fe2+ absorbed directly into duodenum so Fe3+ must first be turned into Fe2+ by ferri-reductase enzymes
- Fe2+ ions bind to ferritin in duodenal cells for storage
- When iron required, Fe2+ turned into Fe3+ by hephaestin
- Fe3+ binds to transferrin for transport where it is delivered to tissue
What is iron deficiency anaemia and give some causes
Anaemia caused by low blood iron (Most common anaemia). Microcytic anaemia
Bowel Cancer
Pregnancy
Blood loss (menorrhagia)
IBS/IDS
Coeliac
H Pylori infection (also proton pump inhibitor use)
Broader causes of iron deficiency anaemia
Increased loss (e.g. chronic GI blood loss) (Most common)
> Colon cancer
> Gastric ulceration
> NSAID/Aspirin use
Malabsorption (Coeliac, helicobacter pylori, gastrectomy)
Increased need (pregnancy, growing children)
Dietary deficiency (rarer)
Signs of iron deficiency anaemia
Pallor
Conjunctival pallor
Atrophic Glossitis (smooth tongue due to atrophy of papillae on surface of tongue)
Koilonychia (spoon shaped nails)
Angular cheilosis (mouth corner ulcers)
Dry rough skin
Dyspnoea, fatigue, headache, restless leg syndrome
Investigations of iron deficient anaemia
1st - FBC -> low MCV, low Hb (MICROCYTIC)
Serum iron
Serum ferritin
Transferrin saturation (serum iron/total iron binding capacity) ALL LOW
TIBC will be high (negative correllation)
Signs specific to iron deficiency anaemia
Pica - Cravings for non food items as food
Hair loss
Restless leg syndrome
Why is acid required for iron absorption?
Stomach acids keep iron in soluble Fe2+ form. When acid drops it changes to Fe3+, which is insoluble
Management of iron deficient anaemia with side effects
Treat underlying cause
Oral iron supplements: ferrous sulphate, ferrous fumarate
Side effects: constipation, diarrhoea, nausea, black stools
Specific anaemia signs that point you places
Iron deficiency
- Koilonychia
- Angular Cheilosis
- Atrophic glossitis
- Brittle hair/nails
Haemolytic anaemia
- Jaundice
Thalassaemia
- Bone deformities
CKD
- Oedema, HTN, excoriations
What should be checked in unexplained iron deficiency
- Colonoscopy
- Oesophogastroduodenoscopy (OGD)
What is pernicious anaemia
Autoimmune B12 deficiency destruction of intrinsic factor (megaloblastic)
Intrinsic factor is secreted by parietal cells and is essential for absorption of B12 in ileum. Antibodies form against intrinsic factor or parietal cells, causing atrophy of gastric mucosa, preventing absorption of vitamin B12.
Other causes of B12 deficiency
Atrophic gastritis (e.g. 2ndary to H pylori), gastrectomy, malnutrition (e.g. alcoholism)
What blood group is more at risk of pernicious anaemia
A
Features of pernicious anaemia
Lethargy pallor dyspnoea + neurological symptoms:
- Pins and needles, numbness, typically symmetrical and affects legs>arms.
- memory loss, poor concentration, confusion, depression, irritability
Investigations in pernicious anaemia
FBC + blood film
- Macrocytic anaemia
- Hypersegmented neutrophil polymorphs and oval macrocytes
B12+folate
Antibitodies
- Anti-IF (intrinsic factor) highly specific but only 50% sensitive
- Anti gastric parietal cell antibodies high sensitivity low specificity
Schilling test (not done routinely anymore)
- Give radiolabelled B12, check absorption. Then give IF and check again if B12 absorption increases
Management of pernicious anaemia
B12 supplement - Oral Cyanocobalamin or IM hydrocobalamin
Folic acid - Never give without B12 - prevent degeneration of the spinal cord
Not a management but it also increases risk of gastric cancer whod have thought
What causes macrocytosis without anaemia
Alcohol!
What does SCT screeninng screen for
Sickle cell
Thalassaemia
Haemoglobin disorders
Define thalassaemia, with epidemiology
Autosomal recessive haemoglobinopathy that causes a microcytic anaemia. Prevalent in areas of malaria (Mediterranean, south Asian, African) as thalassaemia protective against it. (selective advantage)
Either reduction in alpha or beta chains, causing a hypochromic, microcytic anaemia
Pathophysiology and subtypes of alpha thalassaemia
Autosomal recessive, leads to deletions of up to 4 alpha genes on chromosome 16 (2 on each)
1 deletion - Silent carrier (1 or 2, hypochromic and microcytic but normal Hb)
2 deletions - Alpha thalassemia minor/trait. Mild symptoms.
3 deletions - Haemoglobin H (HbH) disease. HbH has 4 beta chains (inability to produce alpha chains). Moderate hypochromic, microcytic anaemia.
4 deletions - Hb Bart’s Hydrops Fetalis syndrome (Alpha thalassaemia major). Hb has high affinity for O2 so tissues not oxygenated. Cardiac failure and massive hepatosplenomegaly causes oedema all over (Hydrops fetalis). Fetus usually dies before birth or in first year.
How does severe hypoxia lead to splenomegaly
Hypoxia causes bone marrow, liver and spleen to increase RBC production. Causes enlargement of liver, spleen and bone marrow.
Pathophysiology of beta thalassaemia
Autosomal recessive point mutations on 2 beta genes on chromosome 11, causing impaired or absent beta chain synthesis.
1 partially or completely defective gene (Bᵀ B) - Beta Thalassaemia Minor (trait). Asymptomatic or mild/absent anaemia with hypochromic and microcytic cells.
2 partially defective genes or 1 and 1 completely defective(Bᵀ Bᴼ). - Beta Thalassaemia intermedia. Moderate anaemia, splenomegaly
2 completely defective genes (Bᴼ Bᴼ) - Beta Thalassaemia Major. Complete absence of beta globin, severe anaemia and lifelong transfusion is needed. Hepatosplenomegaly.
Free alpha chains accumulate in RBCs and damage membrane -> Haemolysis, causing jaundice and secondary haemochromatosis
Why does thalassaemia sometimes not present at birth
HbF still in circulation at first
Signs/symptoms of thalassaemia
- Chipmunk facies (more in beta) - enlarged forehead/cheeks due to extramedullary haematopoiesis
- Hair on end appearance on X ray
- Growth retardation
- Hepatosplenomegaly
- Jaundice
- (OEDEMA IN Hb Barts (Hydrops fetalis))
Anaemia symptoms: Pallor, palpitations, fatigue, failure to thrive
Investigations in thalassaemia
FBC/Blood film - Microcytic, hypochromic anaemia. High iron/ferritin
Blood film: Microcytic hypochromic RBC. Target cells
Hb electrophoresis: HbH (Beta tetramers) in alpha, HbA2 in beta (+low HbA)
Skull X ray: Hair-on-End appearance
Management of thalassaemia
- Blood transfusions
- Iron chellation (oral deferiprone)
- Splenectomy
- Stem cell transplant is only curative option
Complications of thalassaemia
GASH
Gallstones
Aplastic crisis (parvovirus B19)
Secondary haemochromatosis
Hypersplenism
Normocytic anaemia types
Haemolytic
- Sickle cell
- Hereditary spherocytosis
- G6PD deficiency
- Malaria
- Autoimmune haemolysis
Define sideroblastic anaemia with its causes:
Condition where red cells fail to form haem, whose biosynthesis partly occurs in mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around a nucleus caused a ring sideroblast. May be congenital or acquired
Congenital: delta-aminolevulinate synthase-2 deficiency
Acquired
- Myelodysplasia
- Alcohol
- Lead
- Anti-TB medications
Investigations in sideroblastic anaemia
FBC
- Hypochromic microcytic anaemia (more in congenital)
Iron
- High ferritin, iron and transferrin saturation
Blood film
- Basophilic stippling of RBC
Bone marrow
- Prussian blue staining shows ringed sideroblassts
What does Lead poisoning cause defect in
Defective ferrochelatase and ALA Dehydratase function
Features of lead poisoning
Abdominal pain
Peripheral neuropathy
Blue lines on gum margin
Fatigue, constipation, neuropsychiatric features
Investigations in lead poisoning
Blood lead level >10mcg/dL
FBC - Microcytic anaemia.
Blood film - RBC abnormalities, basophilic stippling, clover-leaf morphology
How is lead chelated
Dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
Dimercaprol
Sickle cell pathophys
Autosomal recessive gene mutation on beta globin chain (where valine replaces glutamic acid on 6th amino acid) causes “HbS” variant. (HBB gene on chromosome 11)
Under stress (infection, hypoxia, dehydration, acidosis, cold temperature), RBCs sickle, and HbS polymerises, leading to haemolysis or capillary obstruction (sickle cell crises).
initially, they can return to normal shape but eventually lose membrane flexibility and remain sickled.
Sickle cell relation to malaria
Sickle cell more common in Africa, India, Middle East.
Sickle cell trait (one copy of gene) reduces severity of malaria, causing selective advantage of sickle cell trait in areas with malaria
Classical signs of any haemolytic anaemia
Jaundice, Scleral icterus, gallstones
(caused by haemolysis, releasing bilirubin into the blood)
What are the 4 sickle cell crises
- Sequestration Crisis. RBCs sickle in spleen. Abdominal pain secondary to splenomegaly. Autosplenectomy.
- Aplastic crisis. Infection with parovirus B19 causes bone marrow suppression. causing sudden onset pallor, fatigue, anaemia. Reduced reticulocyte count.
- Haemolytic crisis - jaundice
- Vaso-occlusive crisis - separate card
(+Acute chest syndrome - acute cough, chest pain, dyspnoea)
Signs and symptoms of sickle cell anaemia and of its crises
Anaemia symptoms and jaundice (haemolytic!), worse after stressors
- Various crises, causing autosplenectomy/splenomegaly, bone and chest pain. (NB femoral head susceptible to avascular necrosis)
- Dactylitis
- Priapism
Signs of the vaso-occlusive crises in different areas in sickle cell anaemia.
Bone, ACS, Spleen, CNS, Genitalia
Bone - Dactylitis, Avascular necrosis, osteomyelitis
Lungs - Acute chest syndrome. Dyspnoea, chest pain, hypoxia. New chest infiltrates
Spleen - auto splenectomy, splenomegaly
CNS - Stroke
Genitalia - Priapism - prolonged, painful erection
Investigations for sickle cell anaemia
1st - Newborn screening - guthrie heel prick
- FBC - normocytic anaemia with reticulocytosis (young RBC)
- Blood film - Sickled RBCs, Howell-Jolly bodies
- GOLD: Hb Electrophoresis - HbS chains with absent HbA
- Sickle cell solubility test - HbS insoluble plasma goes cloudy
General management of sickle cell disease
- Hydroxycarbamide (stimulates HbF (foetal haemoglobin), which does not sickle)
- Prophylactic phenoxymethylpenicillin in children
- Pneumococcal vaccine
- Haematopoietic stem cell transplant Last resort
- Blood transfusions (risk of iron overload so iron chellation must be done too)
Define G6PD deficiency
X linked deficiency of Glucose-6-Phosphate Dehydrogenase enzyme, making RBC more susceptible to damage by oxidation
Role of G6PD normally
- Free radicals produced by body which can damage RBCs through DNA, protein and cell membrane damage.
- Glutathione acts as an antioxidant, donating an electron to free radicals, turning them into water and oxygen, but becoming oxidised itself.
- Glutathione reductase uses NADPH to donate an electron back to glutathione and NADP+ is formed.
- G6PD reduces NADP+ back to NADPH using a G6P (which is a metabolite of glucose, so we have lots of it).
Pathophysiology of G6PD
Defective G6PD enzymes produced with shorter half lives, leading to reduced NADPH and glutathione so RBCs are unprotected from free radical damage. Damaged Hb precipitate in cell to form Heinz Bodies and when spleen tries to remove this, it takes a bite out of the RBC, forming bite cells.
Bilirubin from haemolysis is converted to urobilin, giving urine a dark tea-like colour
Common triggers of G6PD
Fava beans
Soy products
Red wine
Metabolic acidosis
Infections (pneumonia, sepsis)
Malaria drugs (chloroquines)
Signs and symptoms of G6PD
Asymptomatic until exposed to oxidative trigger
Jaundice
Dark Tea-coloured urine (urobilin)
Back pain (indicates kidney damage + urine)
Splenomegaly
Anaemia symptoms (Pallor, fatigue, tachycardia, dizziness, palpitation )
Investigations in G6PD
FBC: Low RBC, High reticulocyte
Blood film: Heinz bodies, bite and blister cells
Unconjugated bilirubin: high
GOLD: G6PD enzyme assay
Define hereditary spherocytosis
Autosomal dominant (can be recessive) haemolytic anaemia caused by a defect in spectrin and ankyrin (membrane proteins) causing RBCs to become spherical.
Key signs of hereditary spherocytosis
Neonatal jaundice
Splenomegaly
Anaemia symptoms
Investigations and diagnostic criteria in hereditary spherocytosis
FBC - Normocytic anaemia AND raised MCHC (mean corpuscular haemoglobin concentration)
Blood film - Spherocytes
High bilirubin and urobilinogen
Diagnostic criteria
- Family history
- Typical features
- Positive lab findings (Spherocytes, Raised MCHC)
Treatment of hereditary spherocytosis
Splenectomy
(Lifelong penicillin to prevent post-splenectomy sepsis)
Blood transfusion + Folic acid
3 consequences of intravascular RBC destruction
1) Jaundice - Unconjugated bilirubin in blood
2) Tea-like urine - Unconjugated bilirubin in blood converted to urobilin by liver
3) Kidney disease - Hb broken down to Haemosiderin which is deposited in renal tubular cells
Investigation and treatment in Autoimmune Haemolytic Anaemia
Coombs test positive (agglutination test)
IgG and CD3 = Warm
CD3 alone = cold
Steroids/splenectomy
What is leukaemia
The uncontrolled proliferation of non functional blood blast cells. Leukaemia cells divide rapidly and take up space in the bone marrow, less energy and space available for normal cells. The lack of functioning blood cells leads to leukaemia symptoms, and increased infection and bleeding risk
General leukaemia symptoms
Bone pain, bleeding, bruising, infections, anaemia
- Lymphadenopathy and lymph node pain
- Petechiae (red dots under skin) or petechial rash
- Hepatosplenomegaly
- Easy bruising
- Fatigue
- Weight loss
- Fever
Define acute lymphoblastic leukaemia with epidemiology
Proliferation of lymphoblasts (mostly B cell). Associated with Down syndrome, radiation and t(12;21). Bimodal age distribution, first peak (75% of cases) at 5 years old, second at 50. In T cell ALL, thymus enlargement may be seen
Investigations in ALL
FBC - anaemia, thromocytopenia, leukocytosis (High WBC, low everything else)
Blood film - Lymphoblasts
Nuclear TdT staining - positive
Bone marrow aspiration GOLD - At least 20% bone marrow infiltration
Treatment of ALL
1 - Supportive with blood and platelet transfusions. IV fluids and a hickman line.
2 - Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
First with prednisolone (4-8 weeks then high dose chemo)
Complications of chemotherapy
Stunted growth in children
Tumour lysis syndrome
Infertility
Neurotoxicity
Infections/immunodeficiency
Neutropenia
Investigations in CLL
FBC - anaemia, thrombocytopenia, lymphocytosis
Blood film - Smudge cells (aged or fragile WBCs rupture to leave smudge) + spherocytes if active haemolysis
Flow cytometry - Positive markers for CLL e.g. CD5, CD19, CD20, CD23
Immunoglobulins - Low (B cells dont fully differentiate into plasma cells)
Complications of CLL
Richter transformation - Transformation into a high grade non-Hodgkin lymphoma. (Rapid progressing lymphadenopathy, fever night sweat weight loss (B), raised LDH
Autoimmune haemolytic anaemia
Small lymphocytic lymphoma (Cells move to lymphatic system and settle at nodes)
Hypogammaglobulinaemia
Acute myeloid leukaemia definition, subtypes and epidemiology
Neoplastic proliferation of myeloblasts, with important subtypes;
APML - t(15;17) promyelocyte accumulation with Auer rods. Can cause DIC.
Acute monocytic leukaemia - Monoblast accumulation without Auer rods. Gums infiltrated.
Affects older people, most common over 75s.
Associated with Pataus (trisomy 13), Downs (trisomy 21) syndrome, benzene + radiation exposure
Symptoms specific to AML
Mouth ulcers
DIC (APML)
Gum infiltration/ hypertrophy
Investigations in AML
FBC - Low RBC, platelets. High WBC
Blood film - Blasts and Auer Rods
Bone marrow aspiration - >20% infiltration into bone marrow
Immunophenotyping - checks cell lineage, confirms AML
Management in AML
IV Fluid via hickman line
Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
All-trans retinoic acid in APML, allows blasts to mature into neutrophils
BM transplant
What are Auer rods
Aggregates of myeloperoxidase found in AML that increase risk of clotting (DIC)
Patient with AML suddenly has lots of blood clots, what complication has occured
Disseminated Intravascular Clotting
CML definition and pathophysiology
Uncontrolled proliferation of myeloid cells - usually granulocytes. Associated with t(9;22) - PHILADELPHIA CHROMOSOME.
- BCR-ABL genes fused, permanently activating Tyrosine Kinases, causing proliferation of myeloid cells. Rapid proliferation can lead to Acute Leukaemia (or Blast Crisis)
Phases of CML
Chronic (asymptomatic) <10% blast cells
Accelerated (Further progression) 10-19% blast cells >20% basophils
Blast crisis (terminal phase, mimicks acute leukaemias) >20% blast cells, pancytopenia
Signs of CML
Severe hepatosplenomegaly
Abdominal tenderness/fullness due to hepatosplenomegaly
May show features of gout due to purine breakdown
Investigations in CML
FBC - Very high WCC across spectrum of myeloid cells, low Hb, high Urate
Blood film - Granulocytes
Cytogenetics - Philadelphia chromosome t(9;22)
LDH raised in leukaemia but unspecific
Management of CML
Chemotherapy +- Allopurinol
Tyrosine kinase inhibitor (Imatinib)
Stem cell transplant if severe or if goes to blast phase
Define myelodysplasia/ myelodysplastic syndrome
Dysplasia of myeloblasts in bone marrow but less than 20% infiltration. Causes cytopenia meaning death usually due to infection/bleeding. Increase in blast % causes progression to acute leukaemia
Define lymphoma and give the two types with their differences
Neoplastic proliferation of lymphoid cells (B cells).
- Hodgkins (has Reed-Sternberg cells, spread is contiguous (one node to next) and effects rarely extra nodal)
- Non-Hodgkins (No RS cells, non contiguous spread and goes extra nodal (GI, skin, brain etc)
What type of Hodgkins is most common, what presents with popcorn cells and what is the worst prognosis
Nodular sclerosing MC
Nodular lymphocyte predominant Popcorn cells (RS cell variant)
Lymphocyte depleted has worst prognosis
Risk factors and epidemiology for Hodgkin’s lymphoma
EBV infection history
Family history of lymphoma
Post transplant
HIV
Bimodal (15-35 and >60)
Signs/ symptoms of Hodgkin’s lymphoma
Lymphadenopathy (usually cervical, axillary, inguinal)
- Fixed, hard, rubbery, painless(!). Spread is contiguous
Splenomegaly
Alcohol induces lymph node pain
B symptoms
- Fever, night sweats, weight loss
Pruritus (itching)
Staging/classification used for lymphoma
Ann-Arbor (1,2,3,4/A,B)
1 - 1 region of lymph nodes affected
2 - 2 or more, same side of diaphragm
3 - Involvement on both sides of diaphragm
4 - Widespread involvement including organs
A - No B symptoms
B - B symptoms
Pathology associated with Classical and nodular sclerosing Hodgkin’s lymphoma
Classical - usually painless cervical lymphadenopathy
NS - Mediastinal lymphadenopathy, which may cause cough, chest pain and may compress superior vena cava, dilating neck veins and increaing JVP
Investigations in Hodgkin’s lymphoma
FBC - Low Hb/platelets
CXR - Mediastinal lymphadenopathy and widened mediastinum can be used for Ann Arbor.
PET-CT Scan of thorax/abdomen/pelvis - Staging
Lymph node biopsy GOLD - Reed sternberg cells
Management of Hodgkin’s lymphoma
1A-2A - ABVD chemotherapy
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine
2A-4B - Longer courses of chemotherapy and radiotherapy
Complications of radiotherapy and chemotherapy treatment
Radio - Hypothyroid, lung fibrosis, secondary malignancy
Chemo - Myelosuppression, Nausea, Alopecia, Infertility
Define Non Hodgkin’s lymphoma
All lymphomas without Reed-Sternberg cells. Can spread extra nodally (skin, stomach, GI tract, bone marrow, spinal cord). Usually due to a genetic mutation in lymphocyte.
Signs/symptoms of Non-Hodgkin’s lymphoma
Fixed, hard, rubbery, painless lymphadenopathy. Spread is non-contiguous
May have extra nodal manifestations
Hepatosplenomegaly (more common in NHL)
B symptoms
Fever, night sweats, weight loss
Investigations in NHL
FBC - pancytopenia if BM affected
LDH - Increases as prognosis worsens (increased cell turnover/proliferation)
Lymph node biopsy GOLD - No reed-sternberg/popcorn cells
CXR, PET of chest, abdomen, pelvis - for staging
Lumbar puncture to check for CNS involvement
Treatment of Non-Hodgkin’s lymphoma
Rituximab + Chemotherapy (R-CHVP)
Rituximab (mAB - targets CD20 on B cells)
C - cyclophosphamide
H - hydroxydaunorubicin
V - Vincristine
P - Prednisolone
Intrathecal Methotrexate for prophylaxis
Low grade may not need treatment
Define Multiple Myeloma with epidemiology
Cancer of differentiated B lymphocytes (plasma cells)
70+ years, Afro-Caribbeans
Pathophysiology of Multiple Myeloma
Neoplastic plasma cells release abnormal antibodies consisting only of paraprotein light chains. Light chains can form amyloid proteins, causing amyloidosis. CRAB symptoms
C - Calcium - Hypercalcaemia caused by neoplastic cells releasing cytokines, activating osteoclasts via RANK receptor. Causes bone resorption.
R - Renal insufficiency - nephrocalcinosis and deposition of free light chains (Bence Jones proteins) in kidney tubules disrupt renal function. Results in Bence Jones proteins in urine.
A - Anaemia. Bone marrow infiltration causes reduced haematopoiesis. Pancytopenia
B - Bone pain. Bone lesions, fractures and pain caused by Osteoclast activation, inhibits osteoclast inhibition and suppresses osteoblasts. Common in skull, spine, long bones, ribs.
Signs/symptoms of Multiple myeloma
OLD Crab
70 +
- hyperCalcaemia symptoms: Bones, stones, abdominal moans, psychiatric groans
- Renal insufficiency: Urinary frequency + Bence Jones in urine
- Anaemia - Fatigue, SOB, tachycardia
- B - Bone pain (especially back)
Investigations in Multiple Myeloma
FBC normocytic, normochromic
Blood film - Rouleaux formation
Urine:
- Urine dipstick - Bence Jones protein
- Urine electrophoresis - Paraprotein band or “M” spike (IgG/IgA)
Bone Marrow Aspiration GOLD - >10% monoclonal plasma cells in BM
Imaging:
- Full body MRI to determine BM infiltration and find lesions
- Imaging using CXR - Skull/spine etc. Raindrop skull, Osteolytic lesions
Diagnostic criteria in multiple myeloma
One or more biomarkers
- BM plasma cells >10%
- >1 focal lesion on MRI
- involved : uninvolved free light chain ratio >100
or
CRAB end organ damage
Treatment of Multiple Myeloma
Supportive then. Chemotherapy +- stem cell transplant
- No NSAID (renal impairment)
- Bisphosphonate (suppress osteoclast activity, reduce fracture)
- Anaemia correction
- DVT prophylaxis - LMWH or aspirin
Chemotherapy:
<70 - bortezomib, thalidomide and dexamethasone
>70 - bortezomib, prednisolone and melphalan
Define haemophilia and give its 2 subtypes
Inherited severe bleeding disorders, both affect intrinsic pathway (increase APTT), causing decrease in function or quantity of clotting factors.
A - Deficiency in factor 8
B (Christmas disease) - Deficiency in factor 9
Prolongs clotting time, causing bleeding to be more severe.
What are the causes of haemophilia
Inherited
- X linked recessive (A- F8 gene, B- F9 gene) ∴ mostly affects males!
Acquired
- Liver failure (liver responsible for many clotting factors)
- Vit K deficiency
- Autoimmunity against a clotting factor
- DIC
Signs and symptoms of haemophilia
Spontaneous, excessive, inappropriate bleeding
Nose, gum, GI, urinary, intracranial bleeding for example
Easy bruising
Haemarthrosis (bleeding into joints)
Investigations of haemophilia
PT - normal
APTT - Prolonged (these conditions only affect intrinsic pathway!)
F8/F9 assay to show deficiency
Treatment of haemophilia
A: IV factor 8 + desmopressin (releases F8 stored in vessel walls)
B: IV factor 9
von Willebrand disease definition
Autosomal dominant mutation of vWF gene on chromosome 12 causing deficiency, absence or abnormal functioning of von Willebrand Factor. This causes excessive bleeding
vWF normal function
Basis of platelet plug, attaches to collagen fibres and enables platelet adhesion
Needed as a carrier for Factor 8, protecting it from degradation
von Willebrand disease types
1 reduced/defective vWF
2 Quantity fine but quality affected
2A - unable to bind platelets
2B - binds to platelets in blood, causing thrombocytopenia
2N - Cant bind to factor 8
3 No production
Investigations in vW disease
PT normal
APTT high
Normal F8/F9 (rule out haemophilia)
vWF low
Platelets normal except 2B
Management of vW disease
Desmopressin stimulates release of vWF from Weibelpalade bodies
vWF and factor 8 infusion
What clotting factors rely on vitamin K
10, 9, 7, 2
(1972)
Warfarin MoA
Vitamin K antagonist (affecting factors 10, 9, 7 and 2)
Define thrombocytopenia, and the 2 conditions that cause it
Low platelet count
Immune Thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Define thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura.
Tiny blood clots develop throughout small vessels using up platelets and causing thrombocytopenia, bleeding under the skin and systemic issues.
Pathophysiology of TTP
Problem with ADAMTS13 protein (deficiency or autoimmunity against) means it cannot inactivate von Willebrand factor, which enables platelet adhesion. These clot in small vessels and said clots break up RBCs, causing haemolytic anaemia.
As it affects small vessels, it is known as a microangiopathy
Signs/symptoms of TTP
5 classical symptoms
- Thrombocytopenia
- Microangiopathic haemolytic anaemia
- Fever
- Renal insufficiency causing haematuria and reduced output.
- Neurological symptoms (headache, confusion, seizures, focal abnormalities, coma)
also
Purpuric rash, bleeding.
TTP vs ITP symptoms and how you get it
ITP usually well systematically, rashes and bleeding main symptoms. Acquired
TTP has systematic effects. Inherited
Investigations in TTP
ADAMTS13 decreased
FBC - Thrombocytopenia and normocytic, normochromic microangiopathic anaemia
Blood film - Schistocytes (fragmented blood cells)
Unconjugated bilirubin and LDH raised
PTT/APTT normal
Management of TTP
Plasmapharesis/plasma exchange
Prednisolone + Rituximab (monoclonal antibody against B cells)
How does heparin use cause thrombocytopenia
Heparin induced thrombocytopenia
Antibodies against heparin form, targeting platelet factor 4 protein on platelets.
What is infectious mononucleosis, whats its cause and association
AKA Glandular fever
Caused by EBV and associated with Hodgkin’s, Burkitt’s and nasopharyngeal carcinoma
Presentation of glandular fever
Classic triad
Fever, pharyngitis, lymphadenopathy
Usually presents in adults and young children
Shows atypical lymphocytes on blood film
Investigated with monospot test/agglutination test
How does glandular fever spread and what are its complications
Spread through saliva (kissing, sexual activity)
Lifelong latent infection, can cause chronic fatigue
Causes of TTP
- Post infection (urinary, GI)
- Pregnancy
- SLE
- HIV
What are the types of stye and whats their management
Eyelid infection
- External (hordeolum externum): Infection (usually staph) of the glands of Zeis (sebum producing) or glands of Moll (sweat glands)
- Internal (hordeolum internum): Infection of the Meibomian glands. May leave residual chalazion (Meibomian cyst)
- Management includes hot compress and analgesia. Only Abx if associated conjunctivitis
What is a chalazion
AKA Meibomian cyst. Retention cyst of the Meibomian gland. Presents as a firm painless lump in the eyelid. Majority resolve spontaneously
What are some eyelid problems
Blepharitis: Inflammation of the eyelid margins, causing red eye
Stye: Infection of the glands and eyelids
Chalazion (Meibomian cyst)
Entropion: In-turning of the eyelid
Ectropion: Out-turning of the eyelid
Define benign prostatic hyperplasia
Non malignant growth of the prostate gland, causing compression of the prostatic urethra causing Lower Urinary Tract Symptoms (LUTS). Usually affects stromal and epithelial cells of the transitional zone
Pathophys of BPH
- Luteinising hormone acts on leydig cells to produce testosterone
- 5a-reductase converts testosterone to dihydrotestosterone (DHT)
- Androgens bind to androgen receptors, preventing apoptosis and allowing glandular epithelial cells and stromal cells (connective tissue) to grow.
- With age, testosterone decreases but 5a-reductase activity increases leading to excess DHT, causing excess hyperplasia of the prostate.
- This compresses prostatic urethra, causing build up of urine and difficulty voiding. This also causes bladder hypertrophy.
Causes of fluid overload
Heart or kidney conditions
Pregnancy
Too much salt in diet/too much water intake
Liver failure (hypoalbuminaemia)
Conns
Signs/symptoms of BPH
LUTS Symptoms
Voiding: Hesitancy, weak stream, straining, dysuria, incomplete emptying, terminal dribbling.
Storage: Urgency, frequency, nocturia, incontinence
DRE findings in BPH
Smooth, enlarged, non tender prostate
Investigations of BPH
DRE
PSA Test - Can be raised in BPH, cancer, and fuckin everything else. Shit test, but done for monitoring etc. IPSS (International Prostate Symptom Score)
Pharmacological management of BPH with side effects.
1) Alpha-1-blockers - Tamsulosin (relaxes muscles in bladder to reduce resistance to bladder flow) (SE: Postural hypotension)
2) 5-alpha-reductase-inhibitors - finasteride (inhibit conversion of testosterone to dihydrotestosterone to reduce prostate size) SE: Sexual dysfunction
Surgical management of BPH with main side effect
Transurethral resection of the prostate (TURP)
Main side effect: Retrograde ejaculation, erectile dysfunction
Define prostate cancer with 4 risk factors
Adenocarcinoma of the prostate gland (usually peripheral zone).
Associated with BRCA1 and BRCA2
Age
Afro Caribbean
Family history
Signs/symptoms of prostate cancer
LUTS- Voiding: Hesitancy, weak stream, straining, dysuria, incomplete emptying, terminal dribbling.
Storage: Urgency, frequency, nocturia, incontinence
- Bone pain (if metastasised to bone)
- Wight loss, fatigue, night sweats
Investigations of prostate cancer
DRE: Hard, asymmetrical, nodule, irregular prostate with loss of median sulcus
PSA
Transrectal ultrasound
Prostate Biopsy - GOLD. Used with Gleason score.
Bone scan to check for bone metastasis (Lesions)
What scoring system is used in prostate cancer
Gleason scoring - Uses biopsy to grade prostate cancer
1-5
1 - Well differentiated cancer
5 - Anaplastic (Extremely poorly differentiated)
1st and 2nd most prevalent histological patterns graded and added together to give score out of 10.
Management of prostate cancer
Local - prostatectomy
Active surveillance if >70 or not severe
If metastatic
- Radiotherapy
- Hormone therapy (GnRH e.g. Goserelin) or bilateral orchidectomy (remove testicles) - reduce testosterone
- Androgen receptor blocker
Other causes of raised PSA
BPH
Prostatitis
UTI
Vigorous exercise
Recent ejaculation
What is bursitis
Inflammation of a bursa, small fluid filled sac that cushions and reduces friction between bones, tendons and muscles around the joints.
Common locations for bursitis
- Shoulder (subcromial) - Overhead activities, repetitive arm movement
- Elbow (olecranon) - Leaning on elbows “student’s elbow”
- Hip (trochanteric) - Runners or prolonged standing
- Knee (prepatellar or anserine). Common in people who kneel often
- Heel (retrocalcaneal)
How does bursitis occur and present
Causes:
- Friction from repetitive movements
- Trauma
- Inflammatory arthritis
- Infection (Septic bursitis)
Presentation:
- Swollen, warm, tender, fluid filled
- If infection: Hot, more tender, redness to surrounding skin, fever, features of sepsis.
Consider septic arthritis if reduced ROM
What do the various joint aspiration results suggest
Pus - Infection
Straw coloured fluid - Less likely to be infeced
Blood stained - Trauma, infection, inflammatory cause
Milky - Gout/Pseudogout
Fluid should be sent for MCS
Management of bursitis
Reduce activity of affected joint
Ice
Compression
Elevation
Analgesia
Steroid injections and aspiration may help
Functions of kidney
AWETBED
Acid-base homeostasis
Water balance
Electrolyte balance
Toxin/waste product removal
Blood pressure control
Ertyhropoietin
D (vitamin D activation)
BP Targets in CKD
140/90 or 130/80 if coexisting diabetes
ACEi used (reduce filtration pressure, less proteinuria)
Define AKI
A sudden decline in kidney function leading to a rise in serum creatinine and fall in urine output.
Dysregulation of
- Fluid balance
- Acid-base homeostasis
- Electrolyte imbalance
Drugs to stop in AKI
DAAMN
D - Diuretics
A - ACEi/ARB
A - Aminoglycosides
M - Metformin
N - NSAIDs
ACEi/ARB protective in Chronic
6 pre renal causes of AKI
Hypoperfusion
- Hypovolaemia (bleeding, reduced cardiac output (CHF), cardiogenic shock)
- Liver failure (hypoalbuminaemia)
- Renal artery blockage/stenosis
- ACEi & NSAID
- Sepsis causing systemic vasodilation
- Dehydration
4 intrarenal causes of AKI
Intrinsic disease of kidney
- Acute tubular necrosis
- Acute interstitial nephritis (these 2 can be drug induced)
- Glomerulonephritis
- Small vessel vasculitis
4 post renal causes of AKI
Obstruction to urinary outflow, causing back pressure into kidney. (Obstructive uropathy)
- BPH
- Urolithiasis
- Cervical and prostate cancer
- Bladder neck stricture
Electrolyte consequences of AKI
Hyperkalaemia and azotaemia (increased blood creatinine and urea)
Metabolic acidosis
Symptoms of pre renal AKI
Hypotension
Reduced capillary refill
Dry mucus membranes
Reduced skin turgor
Cool extremities
Intra renal AKI symptoms
Infection/ signs of underlying disease (vasculitis, glomerulonephritis etc)
Post renal AKI symptoms
Loin to groin pain
Haematuria
Palpable bladder/prostate
Prostatic urinary issues (dysuria, terminal dribbling, hesitancy)
Causes of Acute tubular necrosis
Ischaemia - Pre renal disease
Nephrotoxicity - (aminoglycosides, chemotherapy), contrast in CT, myoglobin, multiple myeloma
Define CKD
Progressive deterioration in renal function over at least 3 months characterised by eGFR of <60ml/min/1.73m²
What 2 tests are considered in CKD classification
eGFR and albumin:creatinine ratio
How is eGFR used to stage CKD
Stage 1 - >90 (normal)
Stage 2 - 60-89 (mild reduction, only CKD if symptoms)
Stage 3a - 45-59 (mild-moderate reduction)
Stage 3b - 30-44 (moderate-severe reduction)
Stage 4 - 15-29 (severe reduction)
Stage 5 <15 (End stage kidney failure)
How is albumin:creatinine ratio used to stage CKD
Checks proteinuria to give A score
A1 - <3mg/mmol
A2 - 3-30mg/mmol
A3 - >30mg/mmol
What can be used as evidence of renal damage?
- Albuminuria (ACR>3)
- Electrolyte abnormalities
- Histological abnormalities
- Structural abnormalities on imaging
- Kidney transplant history
- Urine sediment abnormalities
At what eGFR is metformin contraindicated
<30ml/min/1.73² (stage 3b)
Causes of CKD
Most common: Diabetes and HTN
Nephrotoxic drugs
Glomerulonephritis
Systemic disease e.g. rheumatoid arthritis/SLE
How does CKD lead to its complications
low eGFR = azotaemia (which can cause encephalopathy and pericarditis)
Urea affects platelet function (bleeding)
Uremic frost (urea crystals in skin)
Kidneys normally activate vit D. No activation = hypocalcaemia = PTH secretion = bone resorption (renal osteodystrophy)
Low fluid to kidney = RAAS activation = HTN
HTN causing increased intraglomerular pressure - causing shearing and loss of selective permeability (protein/haematuria)
Kidneys produce less EPO = Anaemia
Signs/symptoms of CKD
Asymptomatic at first
Uraemic frost (tiny yellow white urea crystals on skin)
Uraemia swallow (pale/brown colour on skin)
Pallor
Fatigue
Lethargy
Frothy urine
Swollen ankles/oedema
Increased bleeding
What does anaemia, with low calcium and low phosphate imply
CKD
Investigations in CKD
Urine dipstick
- Haematuria, glycosuria
eGFR and urine albumin:creatinine ratio
U&E
FBC
- Normocytic normochromic anaemia
Bone profile/PTH
- Ca2+ low, phosphate high, PTH high, ALP high
Renal ultrasound
Bilateral kidney atrophy (small kidneys)
Complications of CKD
Anaemia (EPO reduced)
Osteodystrophy (decreased vit D activation)
Neuropathy/encephalopathy
Pericarditis
Management of CKD
No cure except transplant, can only treat symptoms
Anaemia - EPO + Iron
Osteodystrophy - Vit D supplementation
CVD - ACEi + statins
Oedema - Diuretics
(ACEi help in CKD but harm in AKI)
What is RRT and what are its indications
Renal replacement therapy - Persistent severe complications (electrolyte, oedema, uraemia) or Stage 5 CKD
AEIOU
Acidosis > 7.2 - Acidosis not helped by sodium bicarbonate
Electrolytes K+>7mmol/L
Intoxication - Stage 5 CKD
Oedema
Uraemic pathology - Encephalopathy, pericarditis etc
What are the types of RRT
Haemodialysis (most common)
- Blood taken from artery, filtered and returned into vein at AV fistula.
- 3x4 hours a week
- Complications: hypotension, nausea, chest pain, infected catheter (sepsis)
Peritoneal dialysis
- Peritoneal catheterisation, exchange of solutes across peritoneal membrane
- Done at home
- Complications: Peritonitis, abdominal wall hernia
Causes of CKD mineral bone disease
Reduced 1-alpha hydroxylase activity (reduced vit D activation)
Reduced renal excretion of phosphate (phosphate stimulates bone resorption)
Treatment of CKD mineral bone disease
Reduced dietary phosphate (fish, meat, poultry)
Vit D replacement (calcitriol is already 1-alpha-hydroxylated)
Phosphate binders
Bisphosphonates
CKD BP targets
140/90 or 130/80 if coexisting diabetes
ACEi used (reduce filtration pressure, less proteinuria)
What are the types of dermatitis, and whats a common cause
Irritant: Common, non allergic. Related to weak acid or alkali exposure. Often seen on hands. Erythema, crusting, vescicles rare
Allergic: T4 Hypersensitivity. Less common. Often seen on head following hair dyes. Acute weeping eczema, predominantly affecting the margins of the hairline, rather than scalp. Potent topical steroid!!!!!!
Cement is a common cause, due to alkaline nature. Dichromates in cement can cause allergic dermatitis too.
Patch testing to differentiate
What is Chronic Fatigue Syndrome
3 months of disabling fatigue, over 50% of the time, in absence of other disease or explanation
Features of Chronic fatigue syndrome
- Sleep problems (not enough, too much, unrefreshing, disturbed)
- Headache
- Joint pain
- Headache
- Painful lymph nodes
- Sore throat
- Dizziness, nausea, palpitations
- Post exertional malaise, worsening symptoms and often slighltly delayed
How is CFS managed
Refer if symptoms >3 months
Energy management
- Manage activities to stay within bounds of energy limit
- NO exercise not overseen by ME/CFS team
- Only if patient feels ready to progress beyond normal daily living
- Graded exercise therapy actively NOT recommended
CBT supportive but not curative
COPD risk factors
- Age (>40)
- Smoking (biggest)
- Air pollution
Occupational exposure (coal, cement, dust, smelting) - Frequent respiratory infections
- Gender (men)
- Alpha 1 anti-trypsin deficiency- (young patients presenting with COPD!!)
O2 saturation targets for a normal person and for someone with an acute COPD exacerbation. And at what O2 sats is someone considered hypoxic
Normal: 95-100%
COPD exacerbation: 88-92% (normal COPD maintained above 92%)
Normal <94%
COPD exacerbation <88%
What 2 organisms usually cause infective exacerbations of COPD
H. influenza
S. pneumoniae
Define chronic bronchitis
Inflammation of the bronchial tubes. Considered chronic when it causes a productive cough for at least 3 months a year for 2 years.
Pathophys of chronic bronchitis
Overall
- Hypersecretion
- Ciliary dysfunction
- Narrowed lumen
Explanations:
- Irritation of epithelium of bronchi causes inflammation. This leads to hypertrophy and hyperplasia of the bronchial mucous glands in bronchi, and goblet cells in bronchioles.
- Epithelial layer becomes ulcerated, eventually replacing the columnar epithelium with squamous (metaplasia), and smoking makes cilia shorter and less mobile
- Chronic inflammation causes infiltration of epithelium, narrowing lumen.
Shortened immobile cilia and narrow, easily blocked lumen predispose to infection
Explain the lung spirometry tests (4)
1) FVC (Forced vital capacity) - Max air volume in 1 breath (<80%)
2) FEV1 (Forced Expiratory Volume in 1 second) - Max air 1 second (<80%)
3) FEV1:FVC Ratio (<0.7 obstructive)
4) TLC (total lung capacity) (increased in COPD due to air trapping)
Signs/symptoms of Chronic bronchitis
Blue Bloater
- Chronic productive cough
- Cyanosis
- Dyspnoea on exertion
- Usually overweight
- Purulent sputum
- Crackles, wheezes when breathing
Hypoxia/aemia (insufficient oxygen in tissues/blood) and hypercapnia (high CO2)
Symptoms of CO2 retention
- Drowsiness
- Asterixis
- Confusion
- Cyanosis
Complications of chronic bronchitis
- 2ndary polycythaemia vera
- Pulmonary HTN due to reactive vasoconstriction to hypoxaemia
- Cor pulmonale due to chronic pulmonary HTN
Define emphysema
Damage to/destruction of the alveolar air sacs. This causes the alveoli to permanently enlarge and lose elasticity. This means the lungs are unable to recoil, so patients have trouble exhaling
Pathophys of Emphysema
Irritants trigger inflammation in lungs, releasing proteases (collagenases, elastases), which break down elastin. Normally, elastin prevents low pressure environment from collapsing. In emphysema, elastin is lost and airways collapse.
This causes:
- Air trapping distal to point of collapse
- Airways stretch during inhalation but cant breath out fully.
- Elastin loss also causes breakdown of thin alveolar walls (Septa), causing neighbouring alveoli to coalesce. This reduces the area for gas exchange.
Types of Emphysema
Centriacinar - most common. Damages central/proximal alveoli in each acinus, in the upper lobes of lungs. Seen in smokers.
Pan-acinar - Whole acinus affected. Seen in A1AT, affecting lower lobes.
Para-septal - Distal alveoli, can cause a pneumothorax when alveoli rupture
Irregular - Irregular acinar involvement. Scarring/fibrosis
Signs/symptoms of emphysema
Pink puffer
- Pursed lip breathing
- Barrel shaped chest
- Hyperresonance on percussion
- Downward displacement of liver
- Dyspnoea, cough, weight loss
Imaging signs emphysema
- Increased anterior-posterior diameter
- Flattened diaphragm
- Increased lung field lucency
Signs of COPD (6)
- Barrel chest
- Hyperresonance on percussion
- Cyanosis
- Pursed lip breathing
- Wheezing/crackling
- Productive cough with purulent sputum
What scale is used to assess breathlessness
MRC dyspnoea scale.
Breathlessness:
1 - on exercise
2 - on hurrying/slight hill
3 - walks slower than others/ has to stop to catch breath
4 - Stops to catch breath after 100m
5 - breathless on minimal activity (getting changed)
Investigations in COPD
Clinical diagnosis - Over 35, smoking history, signs/symptoms of COPD.
Spirometry
- FEV1<80% expected
- FEV1/FVC <0.7, with no bronchodilator reversibility
Chest X ray -
- Flattened diaphragm
- Hyperinflation
- Bullae
CHECK FBC - COPD causes chronic hypoxia -> polycythaemia vera.
How is COPD classified
GOLD classification
Goes down based on FEV1
e.g. FEV1>80% = 1 (mild),
FEV1 50-79 = 2 (moderate) etc
FEV1 49-30 = 3 (Severe)
FEV1 <30 = 4 (very severe)
Name all 5 drugs used in COPD treatment
Bronchodilators:
- Short acting Beta 2 agonist (salbutamol)
- Long acting Beta 2 agonist (salmeterol)
-
- Short acting muscarinic antagonists (Ipratropium bromide)
- Long acting muscarinic antagonists (Tiotropium)
Inhaled corticosteroid (Beclometasone)
Treatment algorithm of COPD (inhalers)
1) SABA or SAMA
2) LABA and LAMA regularly (ICS if asthma features)
3) LABA + LAMA + ICS
+ SABA at any stage (can still be taken as required)
Other treatments of COPD
Long term Oxygen if sats below 92 at rest
Oral Theophylline (bronchodilator)
Oral mucolytic
Prophylactic azithromycin!
How does pulmonary hypertension cause cor pulmonale, and what are its clinical manifestations
Pulmonary vasoconstriction and HTN means right heart must pump against high pressures, eventually failing.
Causes peripheral oedema, raised JVP, hepatomegaly
Complications of COPD (4)
- Cor pulmonale (RH failure secondary to pulmonary HTN)
- Pneumothorax
- Type 1/2 resp failure and respiratory acidosis
- Infections
Define COPD exacerbation with ABG finding
Acute worsening of symptoms, usually due to infective cause (H influenza, S pneumoniae).
Shows respiratory acidosis (low pH and high CO2). Increased bicarbonate (HCO3-) shows compensation by kidney
Treated with amox
What are the criteria for bronchodilator reversibility
> 12% increase in FEV1
AND volume increase >200ml post bronchodilator
Define infective conjunctivitis
Sore, red eyes associated with sticky discharge. Can be bacterial or viral
Bacterial
- Purulent discharge, eyes may be stuck together
Viral
- Serous discharge
- Recent URTI
- Preauricular lymph nodes
How is conjunctivitis managed
Self limiting but can be treated with Abx
- Chloramphenicol drops or ointment
- Drops every 2-3 hours, ointment QDS
- Topical fusidic acid in pregnancy women BD!!
How is conjunctivitis managed in contact lens users
Topical fluoresceins to identify corneal staining
Contact lens should NOT be worn
No school exclusion
What is constipation
Normal bowels: 3x/day-3x/week.
Constipation is bowel movements less than that, with difficult passage or incomplete defecation.
Passage of infrequent hard stools
What are possible complications of constipation
Overflow diarrhoea
Acute urinary retention
Haemorrhoids
Anal fissures
What are some non condition causes and some condition causes of constipation
Non con:
- Low fibre
- Inadequate hydration
- Sedentary lifestyle
- Medication (opioids, antidepressants, antacids and aluminium, certain blood pressure medication)
- Stress
Con:
- Colon cancer (weight loss, blood in stool)
- Intestinal obstruction (scar tissue, strictures, or other blockages)
- Hypothyroidism
- Diabetes
- IBS
Management of constipation
- Exclude impaction
- Lifestyle advice (dietary fibre, adequate fluid, adquate activity)
Medication
1 - Bulk-forming laxatives, ispaghula husk or methylcellulose 1-3 days to effect. Adds bulk, softens stools. Review after 1-2 weeks
2 - Osmotic laxative, macrogol or lactulose
3 - Stimulant laxatives, senna, sodium picosulfate
4 - Specialist treatment, lubiprostone, enema, suppositories etc
What is gout with risk factors
Monosodium urate crystal deposition in joints. MTP most common.
- Elderly
- Male
- Purine rich foods
- Obesity
- HTN
- Impaired kidney function
- T2DM
- Family history
Causes of gout
Increased uric acid production
- Increased cell turnover (leukaemia, haemolytic anaemia)
- Purine rich diet (shellfish, red meat, organ meat)
- Obesity/metabolic syndrome
Decreased excretion
- CKD
- Diuretics/aspirin/pyrazinamide
- Lead toxicity
What foods predispose to gout, what diet is protective
High Purine diet can raise uric acid levels
- Red meat
- Seafood
- Sugary beverages
- Beer
Define Malaria
Notifiable protozoal parasitic infection of Plasmodium genus protozoa
5 protozoa species that cause malaria, and the one that causes complicated malaria
P. falciparum (most common and causes complicated)
P. ovale
P. vivax
P. malariae
P. knowlesi
Spread via female anophales mosquito
Signs and symptoms of malaria
Signs:
- Anaemia
- Jaundice
- Hepatosplenomegaly
- Blackwater fever (malarial haemoglobinuria)
Symptoms:
- Fever
- Chills
- Headache
- Fatigue
- Diarrhoea
- Vomiting
Investigations in malaria
1st and GOLD: blood film
Thick - locates parasites (malaria?)
Thin - identifies Plasmodium species and identifies % of cells infected (species?)
Features of complicated malaria
Cerebral (vascular occlusion, coma etc)
Acute respiratory distress syndrome
Renal failure (proteinuria, haematuria)
Bleeding
Shock
What protozoa most likely to cause relapse in malaria and why?
P ovale and vivax
can form hypnozoites in liver, which emerge later
Preventative measures in malaria
Full body clothing
Insecticide treated bed nets
Prophylaxis (chloroquine) before travel to endemic areas
Indoor insecticide sprays
Empty stagnant collections of water
Treatment of malaria
Complicated: IV artesunate (quinine+doxycycline)
Uncomplicated: Fluids
- Chloroquine - treat acute infection
- Primiquine - kill hypnozoites
What is cerebral palsy
Movement and posture disorder due to a non progressive lesion of motor pathways in developing brain
Causes
- Antenatal: Malformation and congenital infection
- Intrapartum: Birth asphyxia/trauma
- Postnatal: Intraventricular haemorrhage, meningitis, head trauma
Manifestations in Cerebral palsy
Possible manifestations include:
abnormal tone early infancy
delayed motor milestones
abnormal gait
feeding difficulties.
Children with cerebral palsy often have associated non-motor problems such as:
learning difficulties (60%)
epilepsy (30%)
squints (30%)
hearing impairment (20%)
Classifications of cerebral palsy
Classification
spastic (70%)
subtypes include hemiplegia, diplegia or quadriplegia
increased tone resulting from damage to upper motor neurons
dyskinetic
caused by damage to the basal ganglia and the substantia nigra
athetoid movements and oro-motor problems
ataxic
caused by damage to the cerebellum with typical cerebellar signs
mixed
How does horners syndrome present
Miosis (small pupil)
Ptosis (eyelid droop)
Anhidrosis (loss of sweating on one side)
Enophthalmos (sunken eye)
What is normal pressure hydrocephalus
Reversible cause of dementia in elderly patients thought to be caused by reduced CSF absorption at arachnoid villi.
Can be secondary to head injury, SAH, meningitis
Triad:
- Urinary incontinence
- Dementia/bradyphrenia
- Gait abnormality
How is imaging and management completed in Normal pressure hydrocephalus
Hydrocephalus with ventriculomegaly
Managed with ventriculoperitoneal shunting
Complications of diabetes
Diabetic retinopathy
Diabetic nephropathy
Stroke
Cardiovascular disease
Diabetic neuropathy (foot ulcers lead to lower extremity amputation)
Also
- Acute hyperglycaemia leading to crises e.g. DKA/HHS
- Treatment side effects (hypoglycaemia)
Investigations for Diabetes Mellitus
Random plasma glucose >11mmol/L
Fasting plasma glucose >7mmol/L
HbA1C (measures glycated haemoglobin) > 48mmol/L
Oral glucose tolerance test >11mmol/L 2 hours after a 75g oral glucose load (used in borderline/prediabetes cases)
What is the oral glucose tolerance test and what can it help identify?
Fast for 8 hours, take 75g glucose, then glucose measured at intervals. After 2 hours 7.9-11mmol/L indicates prediabetes/impaired glucose tolerance. >11mmol/L indicates diabetes
Helps identify prediabetes, insulin resistance, reactive hypoglycaemia, gestational diabetes
Factors pointing to the 2 diabetes
1
Early age onset
Lean body/ weight loss
High levels of islet autoantibodies
Prone to ketoacidosis
2
Over 30s
Gradual onset
Familial Hypercholestraemia often positive
Hyperglycaemia can be controlled by diet, exercise, oral medication
Signs of Diabetes Mellitus
Acanthosis nigricans (T2DM)
Glycosuria
Ketonuria
Glove and stocking sensory loss
Diabetic retinopathy
Diabetic foot disease (reduced pulses, calluses, ulceration, charcot foot)
What is C peptide
Byproduct of insulin production.
Presence suggests endogenous insulin production
Treatment of type 1 diabetes
Basal bolus insulin
Basal - long acting, maintain stable levels throughout day and overnight (levemir)
Bolus - Fast acting, before each meal, spike insulin (Novorapid)
Complications/side effects of insulin therapy
Lipohypertrophy at site of injection
Hypoglycaemia [main one!]
Weight gain due to feeling more hungry
Insulin resistance
What is assessed at an annual diabetes review?
Retinopathy
Diabetic foot problems
CVD risk factors
Nepthropathy (eGFR, Albumin:Creatinine ratio)
Treatment of Type 2 diabetes
1st - Metformin (class is biguanides)
2nd - SGLT2 inhibitor (empagliflozin) or DPP-4 inhibitor (linagliptin) or GLP1 analogue (liraglutide) Dual Therapy W/ metformin
3rd - Triple therapy
4 - + Basal insulin
MoA and side effects of metformin
Decreases gluconeogenesis, and increases peripheral utilisation of glucose (only acts in presence of insulin)
Side effects: nausea/vomiting, abdominal pain, diarrhoea, altered taste
VITAMIN B12 DEFICIENCY
MoA of SGLT-2i
Sodium-glucose co-transporter-2 inhibitors. Block reabsorption of glucose in kidney, increasing glucose excretion
Side effects: Dehydration, UTI, genital thrush
Side effects of DPP4 i
Stomach pain, nasopharyngitis,
upper resp tract infection, hypoglycaemia when taken with other medication
MoA of GLP1 analogues
MoA: Binds to and activate GLP-1 (glucagon like peptide 1) receptor, increases insulin secretion, suppresses glucagon secretion, slows gastric emptying
SE: Decreased appetite and weight loss, headache, dizziness, dry mouth
Give the classification of hypoglycaemia
Level 1: Plasma glucose<3.9mmol/L
Level 2: Plasma glucose<3mmol/L
Level 3/Severe: Impaired cognitive function sufficient to need extra help to recover
Signs/symptoms of hypoglycaemia
Autonomic: Trembling, palpitations, sweating, hunger
Neuroglycopenic: confusion, weakness, drowsiness, vision changes, nausea, headache
Hypoglycaemia driving rule
More than 1 episode of hypoglycaemia whilst awake or 1 whilst driving = Tell DVLA immediately. License is revoked but can reapply after 3 months
How many GLUT (glucose transporter) channel proteins are there and what are their functions
GLUT-1: Non insulin stimulated glucose uptake
GLUT-2: Found in beta-cells of pancreas, enabling them to sense glucose levels. High affinity transporter; only allow glucose in when concentration is high, when insulin needs to be released. Also found in kidney and liver.
GLUT-3: Non insulin mediated glucose uptake into brain, neurons, placenta
GLUT-4: Mediates peripheral action of insulin, glucose taken up into muscle and adipose tissue after insulin stimulation
Signs/symptoms, and electrolyte change associated with diabetic ketoacidosis
Signs:
- fruity smell of acetone on breath
- Kussmaul breathing (rapid, deep - compensatory mechanism to blow off CO2, reduce acidity)
- Reduced tissue turgor
- Hypotension
Symptoms:
Diabetes symptoms + abdominal pain, nausea/vomiting, confusion, leg cramps
- Hyperkalaemia
What are the diagnostic criteria for diabetic ketoacidosis? What shows up in urine and what electrolyte dysfunction does it cause
Ketonaemia >3mmol/L
Hyperglycaemia >11mmol/L (RPG)
Acidosis <7.3pH
Also find:
Ketonuria/ Glycosuria
Hyperkalaemia common, but hypokalaemia suggests severe DKA
Treatment of diabetic ketoacidosis
ABCDE (emergency)
IV fluids (0.9% saline)
Insulin infusion
Potassium monitoring, replacement may be needed.
Anticoagulant
Define hyperosmolar hyperglycaemic state with pathophysiology
Complication of type 2 diabetes usually triggered by precipitant. Hyperglycaemia leads to osmotic diuresis in kidneys, with loss of sodium and potassium, and severe dehydration.
This leads to hyperglycaemia, hyperosmolality (Thick blood) and hypovolaemia.
No ketosis as insulin sufficient to prevent it
Signs and symptoms of Hyperosmolar Hyperglycaemic State
Signs -
- Reduced consciousness/GCA
- Dehydration!
- Tachycardia
- Hypotension
- Reduced tissue turgor
Symptoms - Polyuria/polydipsia + confusion, cramps, visual disturbances, headache
(Slower onset than DKA)
Investigations and main findings in Hyperosmolar Hyperglycaemic State.
AND Treatment
Glucose, ABG, Blood ketone level, serum osmolality, U&E (monitor electrolyte levels)
Will show Hyperglycaemia, hyperosmolality and hypovolaemia.
NO Ketonuria or ketonaemia
Treatment:
1 - IV Fluid (0.9% saline)
2 - Insulin (potassium/glucose maybe too)
3 - LMWH may also be needed (as blood is thicker)
4 - Potassium replacement may also be needed
What are 5 primary causes of hyperthyroidism?
Graves disease (75-80% cases) (Autoimmune)
Toxic multinodular goitre
Toxic adenoma (thyroid adenoma)
Ectopic T3/T4 production
De quervains (post-viral - painful goitre!)
(drugs separate card)
Drug causes of hyperthyroidism (4)
Lithium
Iodine
Amiodarone (Anti-arrhythmic drug can cause hypo and hyper)
Levothyroxine (hypothyroid treatment causing iatrogenic hyperthyroidism)
Secondary causes of hyperthyroidism
Pituitary adenoma secreting TSH
Ectopic tumour secreting TSH
Hypothalamic tumour secreting TRH (thyrotropin releasing hormone)
What cause a diffuse or nodular goitre?
Diffuse:
- Graves, Hashimoto’s, De Quervains (Only PAINFUL goitre!!)
Nodular:
- multinodular goitre, Carcinoma, Adenoma (SOLITARY NODULE)
Symptoms of hyperthyroidism (with pneumonic)
Everything speeds up!
THYROIDISM
Tremor
Heart rate increase (tachycardia)
Yawning
Restlessness
Oligomenorrhoea
Irritability
Diarrhoea
Intolerance to heat
Sweating
Muscle wasting (WEIGHT LOSS)
Key others include
Reduced libido
Weight loss
Palpitations
General Hyperthyroid signs (5)
Goitre
Lid lag
postural tremor
hyperreflexia
sinus tachycardia
5 Graves specific signs
Diffuse goitre
Thyroid bruit
Thyroid eye disease (Exophthalmos + Ophthalmoplegia (bulging eyes + paralysed eye muscles))
Pretibial myxoedema (lesions on shins)
Acropachy (thick extremities)
Investigations for hyperthyroid diseases
1st - Thyroid Function Test
- TSH low, T3/T4 high in Primary (e.g. Graves’)
- TSH high, T3/T4 high in Secondary
- If TSH high/low, T3/T4 normal, subclinical hypo/hyper
2nd - Antibodies
TSH receptor antibodies (TRAb) high in Graves’
Anti-TPO - both Graves and Hashimoto’s (which is HYPO)
Treatment of hyperthyroidism
1 - Carbimazole (class - thionamides) Decreases synthesis of new T4.
- Block and replace regimen with levothyroxine (T4) in Graves when EUTHYROID (normally functioning). (Propylthiouracil if contraindicated)
2 - Radioiodine (131I). Direct ionisation of thyroid cells.
3- Thyroidectomy (partial if possible/needed)
Side effects of Carbimazole and surgery for thyroidism
Carbimazole. (TERATOGENIC)
Common: Rash
Severe: Agranulocytosis (sore throat, fever, mouth ulcers
Surgery
Hypothyroidism, laryngeal nerve palsy
What is thyroid storm and how is it treated
Hypermetabolic state caused by excess T3/T4.
Occurs secondary to factor such as trauma or infection, or suddenly stopping meds.
Acutely worsened temp, tachycardia, reduced GCS, nausea/vomiting, abdo pain/diarrhoea
Management of thyroid storm
IV Fluid, NG tube if vomiting
Propylthiouracil 1st
IV hydrocortisone
Propanolol also given
Oral iodine >1hour after propylthiouracil
Main causes of hypothyroidism
Hashimoto’s thyroiditis (most common developed nations)
Iodine deficiency (most common worldwide)
Post partum (self limiting, autoimmune, resolves in 12 months)
Drugs
Secondary to hyperthyroid treatment (Carbimazole, propylthiouracil, Radioiodine, surgery)
Secondary to pituitary failing to produce TSH (often associated deficiency e.g. ACTH.)
Presentation of hypothyroid
Everything slows. (BRADYCARDIC)
Bradycardia
Reflexes reduced
Ataxia
Dry hair/skin (+queen annes sign + hair loss)
Yawning
Cold peripheries and constipation
Ascites and oedema (fluid retention)
Round face
Depression/lethargy/fatigue
Immobile
Congestive heart failure
Others:
Goitre
Carpal tunnel
Cold intolerance
Weight gain!!
What is lyme disease
Caused by spirochaete Borrelia burgdorferi and spread by ticks.
<30 days
- Bulleye rash (erythema migrans), usually 1-4 post bite. Painless, >5cm and slowly grows.
- Headache, lethargy, fever, arthralgia
> 30 days
- Heart block, peri/myocarditis, meningitis
Investigation and management of lyme disease
Can be diagnosed if erythema migrans (bullseye rash) seen
ELISA Antibodies to Borrelia burgdorferi
Managed with tick removal (tweezer) and washing.
If Lyme disease, doxycyline, with amox as alternative
Jarisch-Herxheimer reaction (fever, rash, tachycardia, after first dose) possible
