Medix

  Background Pathophysiology Autosomal recessive mutation leading to absence or dysfunction of the α or β globin chains on the haemoglobin A (HbA) molecule. α-thalassaemia leads to impaired oxygen transport and extravascular haemolysis (via splenic clearance). β-thalassaemia leads to failed erythropoiesis, with the build up of α chains causing cell destruction. Compensatory erythroid hyperplasia (↑immature RBCs) causes bone growth. Severity of disease reflects how many alleles are affected: out of 4 for α (which has 2 genes), and out of 2 for β (just 1 gene). Symptomatic and asymptomatic states Asymptomatic carrier states: β-thalassaemia trait (aka minor): 1 β allele affected. α-thalassaemia silent carrier (aka minima), with 1 allele affected, or α-thalassaemia trait (aka minor), with 2 alleles affected. In α or β thalassaemia minor/trait, microcytic anaemia may be the only sign. Symptomatic disease: β-thalassaemia: homozygous for partly functioning alleles (thalassaemia intermedia...

  Background Pathophysiology Autosomal recessive mutation in gene for the β-globin chain of haemoglobin. Leads to an abnormally-shaped sickle cell haemoglobin (HbS), which (a) breaks down easily (haemolytic anaemia), (b) occludes the microvasculature, and (c) is sequestered in the liver and spleen, the latter causing splenic dysfunction and immunosuppression. Lifespan of HbS is 20 days vs. 120 days of normal haemoglobin (HbA). Homozygous (HbSS) inheritance causes sickle cell disease (aka sickle cell anaemia), while heterozygous (HbAS) sickle cell trait is usually an asymptomatic carrier state where most haemoglobin is HbA. Other forms of sickle cell disease: HbS plus Hb C-E (compound heterozygotes), HbS plus thalassaemia. Epidemiology 1/2500 UK newborns have sickle cell disease. 1/200 UK Afro-Caribbeans have sickle cell disease, 1/10 are carriers. Also increased risk if Middle Eastern, Mediterranean, or Indian. Signs and symptoms Chronic features: Haemolytic anaemia: pallor, fatigu...

  Background Anaemia due to lysis of red blood cells. Can be acquired or inherited: Acquired: immune or non-immune mediated. Inherited: RBC metabolism defects, RBC membrane defects, abnormal Hb production. Can be extra- or intra-vascular: Extravascular haemolysis occurs via removal of defective or antibody-tagged RBCs from circulation, primarily in the spleen. Intravascular haemolysis can result from microangiopathic haemolytic anaemia (MAHA), G6PD, paroxysmal nocturnal haemoglobinuria (PNH), or ABO incompatible transfusion. Acquired haemolytic anaemia Immune-mediated (DAT +ve) Warm autoimmune haemolytic anaemia: Usually primary (idiopathic). Can also be secondary to SLE, RA, CLL, or lymphoma. 'Warm' refers to the temperature at which the antibodies (IgG) bind RBCs (37°C). Cold autoimmune haemolytic anaemia: Aka cold agglutinin disease. Less common than warm AIHA. Primary (idiopathic) or secondary to lymphoproliferation (CLL, lymphoma, Waldenström's) or infection ( Mycoplas...

  Background Overview Definition: failure to conceive despite regular unprotected intercourse. WHO defines it as 1 year, NICE used to define it as 2 years (but now doesn't specify). Investigate couples who are having difficulty after 1 year of trying. 85% of people conceive within 1 year, and 92% within 2 years. 50% are due to female causes, 30% male, and 20% unexplained. Sometimes both male and female causes are present. Female causes Usually ovulatory – commonly PCOS – or tubal – commonly PID or endometriosis. Age is the most important determinant of fertility. Declines steeply in late 30s. Ovulatory: WHO class 1 (HPO failure → hypogonadotrophic hypogonadal): anorexia nervosa, intense exercise, Kallmann syndrome (congenital ↓GnRH, anosmia). WHO class 2 (normogonadotrophic normoestrogenic): mainly PCOS, which causes 90% of anovulatory infertility. WHO class 3 (primary ovarian failure → hypergonadotrophic hypoestrogenic): amenorrhea including premature menopause, radiation or chemo...

  Background Definition Acute (<1 week), new onset, abdominal pain. Causes Inflammation: appendicitis, diverticulitis, cholecystitis, gastroenteritis, salpingitis (PID), inflammatory bowel disease, pyelonephritis. Rupture/perforation: spleen, abdominal aortic aneurysm, peptic ulcer, appendix, bowel, gallbladder, ectopic pregnancy, ovarian cyst. Bowel obstruction. Bowel ischaemia. Torsion and strangulation: strangulated hernia, ovarian cyst torsion, testicular torsion. Chest: lower lobe pneumonia, inferior MI. Others: renal colic, endometriosis, adhesions. Signs and symptoms Visceral (organ) pain: Poorly localised. In the context of an obstructed viscus or lumen, may cause colic as waves of peristalsis push against obstruction. Foregut structures – from lower ⅓ of oesophagus to ampulla of Vater – cause epigastric pain. Midgut structures – up to ⅔ of transverse colon – cause umbilical pain. Hindgut structures – up to proximal rectum – cause suprapubic pain. Parietal pain (peritoni...