Pathology Flashcards
What are the signs of a shocked patient
Pale, cold, clammy skin (peripheral vasoconstriction) Sweating rapid, shallow breathing (tachypnoea) Weakness and dizziness Hypotension (can be postural) tachycardia feeling sick and possibly vomiting Thirst Pyrexia in sepsis Oliguria (indicator of kidney function)
What is the treatment of choice for acute shock
Treatment with synthetic colloids as immediate fluid of choice and also need to treat the underlying cause
How can the red cell membrane get damaged
Mechanical damage (e.g. passing through a damaged valve)
Deposition of fibrin in small blood vessels causes mechanical damage (seen in E. coli 0157)
Inherited membrane defects (hereditary spherocytosis etc)
Autoimmune or alloimmune reactions
Inflammation
Oxidative stress
What is a spherocyte
Abnormal RBC
Its membrane is tight, and the biconcave shape has been lost (circular)
Still contains the same amount of Hb
Why are red blood cells more vulnerable to oxidative damage
Due to their close relationship with oxygen binding, as well as the dangers of oxidised iron
Also linked to water so can easily form H2O2
What happens to the red cells in spherocytosis
The RBCs are spherical rather than biconcave
Genetic defect leading to structural problems with the red cell membrane
The membrane can get stripped off as it struggles to squeeze through the vessels
The blood cell becomes smaller and spherical to try and protect itself
Spleen will become enlarged as it tries to cope with getting rid of the damaged cells
How do you treat hereditary spherocytosis
Long term treatment involves splenectomy
Can give folic acid
Treat the underlying trigger – infection
What are the signs and symptoms of spherocytosis
Intermittent jaundice and fatigue
Can be triggered by infections
Folate deficiency
What are the main form sof haemoglobin
HbA - 2A and 2B chains
Most common form in adults
HbA2 - 2A and 2delta chains
Seen in B-thalassaemia
HbF - 2A and 2gamma chains
Foetal Hb
On which chromosome are the alpha globin genes found
Chromosome 16
There are 2 alpha genes per chromosome
Therefore 4 per cell
On which chromosome are the beta globin genes found
Chromosome 11
There is 1 beta gene per chromosome
Therefore 2 per cell
At what age are the adult level of Hb reached
6-12 months
Therefore beta chain issues don’t present until then (still have function HbF until then)
What are haemoglobinopathies
Hereditary conditions affecting globin chain synthesis
Includes thalassemia’s (make less globin) and structural Hb variants
What type of inheritance do haemoglobinopathies follow
Autosomal recessive
To have a condition you generally have to have inherited two copies
If you only get one copy, you have the trait or carry it
What is affected in alpha thalassaemia
The alpha globin chains
What is affected in beta thalassaemia
The beta globin chains
What is thalassaemia
Reduced globin chain synthesis resulting in impaired haemoglobin production
Leads to a microcytic hypochromic anaemia
Can have toxic accumulation of globin chains and haemolysis
What causes alpha thalassaemia
Results from deletion of one or both alpha genes from chromosome 16
If one its called A+
If both its called A0
Which types of Hb are affected by alpha thalassaemia
All types - HbA, HbA2 and HbF
Alpha chains are present in all of them
What are the different classifications of alpha thalassaemia
α thalassaemia trait; one or two alpha genes missing
HbH disease; only one alpha gene left
Hb Barts hydrops fetalis; no functional α genes
Describe alpha thalassaemia trait
Asymptomatic carrier state
May have microcytic, hypochromic red cells with mild anaemia
Don’t really need treatment
Describe HbH disease
Type of alpha thalassaemia with only one working gene Common in SE Asia
Will present with anaemia with very low MCV and MCH
Jaundice, splenomegaly, may need transfusion
What happens to B globin chains in HbH
Excess β chains form tetramers (β4) called HbH
B chains want to bind to something – if you don’t have A chains due to thalassemia then they bind to each other
This is non-functional
Which ethnicity has a high incidence of a-thalassaemia
SE Asian
Higher risk of more severe forms if both parents from Se Asia
What are the clinical features of Hb hydrops foetalis syndrome
Profound anaemia
Cardiac failure
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Almost all die in utero - incompatible with life
What type of Hb is affected by B-thalassaemia
Only HbA
This is the only type that contains B chains
Therefore can make foetal Hb but not adult
What type of mutation usually causes B thalassaemia
Point mutations
What can cause iron overload
Hereditary haemochromatosis - primary
Secondary - transfusional and iron loading anaemias
What causes hereditary haemochromatosis
Mutations in the HFE gene
Decreases synthesis of hepcidin
Increased iron absorption and gradual accumulation
What are the clinical features of hereditary haemochromatosis
Weakness/fatigue Joint pains Impotence Arthritis Cirrhosis Diabetes Cardiomyopathy May be asymptomatic until end organ damage has occurred
When does hereditary haemochromatosis usually present
In middle age or later
Very gradual process
How do you diagnose hereditary haemochromatosis
Genetic test - look for mutations
Transferrin saturation - increased
Serum ferritin - increased
Liver biopsy
How do you treat hereditary haemochromotosis
Weekly venesection
Keep doing it until you get their iron stores low enough
Then repeat a few times a year to prevent it rising again
Family screening
What can cause an iron loading anaemias
Repeated red cell transfusions
Excessive iron absorption related to over-active erythropoiesis - thalassaemia, sideroblastic anaemia
Red cell aplasia
How can you treat secondary iron overload
Iron chelating agents
Desferrioxamine (subcut or IV infusion)
They bind to iron and form a complex that is then excreted to reduce iron load
Why can you not treat secondary iron overload with venesection
The patients are usually already anaemic
What are the classifications of B thalassaemia
β thalassaemia trait - asymptomatic carrier trait
β thalassaemia intermedia - moderate severity
β thalassaemia major - unable to make adult Hb
What is the difference between β+ and β 0
β+ will have reduced β chain production
β0 will have absent chain production
How does β thalassaemia present
Presents aged 6-24 months (as HbF falls) Pallor, failure to thrive Extramedullary haematopoiesis causing; Hepatosplenomegaly Skeletal changes - marrow expands Organ damage
How do you manage β thalassaemia major
Regular transfusion programme to maintain Hb at 95-105g/l
This suppresses ineffective erythropoiesis and inhibits over-absorption of iron
Bone marrow transplant may be an option
What are the consequences of iron overload
Endocrine dysfunction - impaired growth and puberty, diabetes, osteoporosis
Cardiac disease - cardiomyopathy, arrhythmias
Liver disease - cirrhosis, hepatocellular cancer
What can cause sickle cell disorders
Point mutation in codon 6 of the β globin gene
This alters the structure of the resulting Hb which distorts the red cell
Describe sickle cell trait
One normal, one abnormal β gene
Asymptomatic carrier state
May sickle in severe hypoxia eg high altitude, under anaesthesia
Blood film normal
What is the issue with sickle cells
HbS polymerises if exposed to low oxygen levels for a prolonged period
What causes sickle cell anaemia
Two abnormal β genes
HbS will be over 80% with no HbA
What happens in sickle cell anaemia
Episodes of tissue infarction due to vascular occlusion – sickle crisis (very painful)
Chronic haemolysis – shortened RBC lifespan
Sequestration of sickled RBCs in liver and spleen
Hyposplenism due to repeated splenic infarcts
What can precipitate a sickle crisis
Hypoxia Dehydration Infection Cold exposure Stress/fatigue
What happens in a sickle crisis
Tissue ischaemia due to the sickle cells occluding vessels
Leads to pain in that area
How do you treat sickle crisis
Opiate analgesia Hydration Rest Oxygen Antibiotics if evidence of infection Red cell exchange transfusion in severe crisis eg (lung) chest crisis or (brain) stroke
What is the long term management of sickle cell anaemia
Prophylactic penicillin and vaccinations due to hyposplenism
Folic acid supplementation
Hydroxycarbamide - induces HbF production which can reduce severity
Regular transfusion to prevent stroke in some patients
How do you diagnose haemoglobinopathy
FBC; Hb, red cell indices
Blood film
Ethnic origin
High performance liquid chromatography (HPLC) or electrophoresis to quantify haemoglobins present
What is compensated haemolysis
Increased red cell destruction compensated by increased red cell production
Some patients’ are able to compensate so aren’t anaemic
What happens when haemolysis cannot be compensated for
Haemolytic anaemia
The Hb falls
Bone marrow cant keep up
What are the sequelae of haemolysis
Erythroid hyperplasia (increased bone marrow red cell production) Excess red cell breakdown products eg billirubin
How can you detect haemolysis
Increased red cell production
Detection of breakdown products
What is the normal bone marrow response to haemolysis
Reticulocytosis
Erythroid hyperplasia
What is extravascular haemolysis
The blood cells are taken up by the spleen and liver (reticuloendothelial system)
What is intravascular haemolysis
Red cells destroyed within the circulation
They spill their contents into the bloodstream
Which type of haemolysis is more common
Extravascular
What are the signs of extravascular haemolysis
Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
Unconjugated bilrubinaemia which leads to jaundice and gall stones
Urobilinogenuria - bilirubin in the urine
