Yellow normocytic anaemia Flashcards
What is malaria
Malaria is a parasitic infection caused by protozoa of the genus Plasmodium.
Epidemiology of malaria
- Malaria is a serious global health problem that affects millions of people, particularly:
- Young children under the age of 5
- Pregnant women
- Patients with other health conditions like HIV and AIDS
- Travellers who have had no prior exposure to malaria
Tropical and subtropical countries
Most severe is plasmodium falciparum
Aetiology of malaria
Protozoa of plasmodium genus:
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium ovale
- Plasmodium knowlesi
Pathophysiology of malaria
Malaria is spread through bites from the female Anopheles mosquitoes that carry the disease.
Once the plasmodium gets into the bloodstream, it starts to infect and destroy mainly liver cells and red blood cells, which causes a variety of symptoms and sometimes even death.
Active infection of malaria
incubation time, which is the period of time between infection and symptom onset
Plasmodium falciparum incubates for a few days, whereas Plasmodium malariaieincubates for a few weeks.
release of tumour necrosis factor alpha and other inflammatory cytokines, causes fevers that typically occur in short bursts, and correspond to the rupture of the infected red blood cells
Malaria causes haemolytic anaemia - what are the symptoms?
- extreme fatigue,
- headaches,
- jaundice
- splenomegaly
What do most plasmodium infections have?
mild course of symptoms and are generally regarded as uncomplicated malarial infections. These typically resolve with treatment.
What is recurrent malaria?
After recovery, some individuals can get symptoms after a period of time and divided and into 3 underlying causes recrudescence, relapse, and reinfection.
What are the 3 causes of recurrence in malaria?
- Recrudescence refers to ineffective treatment that didn’t completely clear the infection
- Relapse refers to situations where the blood was cleared of merozoites but hypnozoites persisted in the liver, and then emerged to cause more problems
- Reinfection is when an individual was effectively treated, but a completely new infection caused a new bout of malaria
What does plasmodium falciparum do? (complicated malaria)
known for causing the worst infections.
PF generates a sticky protein that coats the surface of the infected red blood cells.
protein causes the red blood cells to clump together and occlude tiny blood vessels - a process called cytoadherence.
Causes organ failure
Signs of malaria
- Pallor: due to anaemia
- Jaundice: due to unconjugated bilirubin from destruction of RBCs
- Hepatosplenomegaly: due to compensation for anaemia
Symptoms of malaria
- Fever, sweats and rigors (occurs in spikes)
- Fatigue: due to anaemia
- Headaches
- Myalgia
- Vomiting
Investigations for malaria
- FBC, U&E, LFT: thrombocytopenia, elevated lactate dehydrogenase levels due to haemolysis, and normochromic, normocytic anaemia
- Malaria blood film: will show the parasites, the concentration and also what type they are.
Management of uncomplicated malaria
- Artemether with lumefantrine (Riamet)
- Proguanil and atovaquone (Malarone)
- Quinine sulphate
- Doxycycline
Complicated or severe malaria management
IV:
- Artesunate: this is the most effective treatment but is not licensed.
- Quinine dihydrochloride
Prevention of malaria:
- Full body clothing
- Mosquito repellent
- Sleeping in insecticide covered mosquito nets
- Indoor insecticide sprays
- Clean water
- Use antimalarials e.g. malarone, mefloquine, doxycycline
Complications for complicated malaria
- Cerebral malaria: altered mental status, seizures and coma
- Bilious malaria: diarrhoea, vomiting, jaundice and liver failure
- Acute kidney injury
- Pulmonary oedema
- Disseminated intravascular coagulopathy (DIC)
- Severe haemolytic anaemia
- Multi-organ failure and death
What is the definition of Hereditary spherocytosis (HS)?
inherited haemolytic anaemia and is autosomal dominant in the majority of cases (75%), but can also be autosomal recessive.
Epidemiology of HS
- HS is the most common genetic haemolytic disease.
- It is more common in Northern Europe and North America but can affect people of any race.
- It is diagnosed in 1 in 2000 people, whilst a large proportion of these individuals are asymptomatic
RFs for HS
- amily history
- Northern European descent
Why does HS occur?
Defect in red cell membrane proteins (ankyrin + spectrin) > causes RBC to lose biconcave shape and become spherical > leads to accelerated degradation of RBCs in spleen resulting in normocytic anaemia
Why does splenomegaly occur in HS?
spleen has to work harder (hypersplenism) to clear out the abnormal RBCs and their products.
What happens as haemolysis occurs
Patients can have episodes of haemolytic crisis, often triggered by infections, where the haemolysis, anaemia and jaundice is more significant.
Patients with HS can have aplastic crisis - what is this?
During aplastic crisis there is increased anaemia, haemolysis and jaundice, without the normal response from the bone marrow of creating new red blood cells. This is often triggered by infection with parvovirus.
S+S of HS
Splenomegaly
Pallor
Jaundice
RUQ pain
Failure to thrive
Fatigue
1st line investigations for HS
-
FBC:normocytic anaemia with an increased reticulocyte count and raised MCHC
- MCHC is increased as spherical RBCs lead to water diffusing out of the cell
- Blood film:spherocytosis
- LFTs:increased (unconjugated) bilirubin due to haemolysis
-
Coombs test: - important
No tests needed if FH of HS + Typical clinical features
Management of HS
Phototherapy transfusion
Blood transfusion
Folic acid
Splenectomy - reduces haemolysis
Complications of HS
Gallstones
Aplastic crisis
Bone marrow expansion
Post- splenectomy sepsis
What is G6PD deficiency?
G6PD deficiency is a condition where there is a defect in the G6PD enzyme normally found in all cells in the body.
Epidemiology of G6PD
- t is inherited in an X linked recessive pattern, meaning it usually affects males.
- It is more common in Mediterranean, Middle Eastern and African patients.
- 6DPD deficiency can be protective against malaria
RFs for G6PD deficiency
Soy products
Fava beans
Red wine
Metabolic acidosis
Medications - sulfonyureas, trimethoprim, nitrofurantoin
What is G6PD mutation caused by?
G6PD gene which is found on the X chromosome and thus it’s an X-linked recessive genetic condition and it almost exclusively manifests as a disease in men.
What do low levels of G6PD lead to
auses low levels of NADPH, leading to low levels of reduced glutathione.
G6PD is the only way for red blood cells to get NADPH so they are especially susceptible to damage caused by free radicals.
When FR build up cell mem becomes unstable causing haemolysis
Free radicals damage Hb, what does it do?
Damaged Hb precipitates inside cells and called Heinz bodies
spleen macrophages notice these Heinz bodies and try to remove them by taking a chunk out of the cells, leaving these red blood cells partially devoured. These are known as bite cells.
When haemolysis occurs what happens?
this leads to conversion to bilirubin, which can result in jaundice and further complications e.g. gallstones. Some of the bilirubin is converted to urobilin, which builds up to give the urine a dark tea-like colour. This could cause damage to the kidneys
S+S OF G6PD deficiency
Jaundice
Pallor
Splenomgealy
Dizziness
SOB
Headaches
Investogations of G6PD
- FBC: low levels of RBC, high reticulocytes
- Blood film: heinz bodies and bite cells
- LDH: elevated
- Bilirubin: elevated
- Haptoglobin: low
- Coomb’s test: negative (used to detect immune mediated anaemias)
- Diagnosis can be made by doing aG6PD enzyme assay
Management of G6PD
- Avoid trigger of haemolysis e.g. fava beans and certain medications
- In certain cases, transfusions may be needed
Definition of sickle cell anaemia
Sickle cell anaemia is an autosomal recessive mutation in the beta chain of haemoglobin, resulting in sickling of red blood cells (RBCs) and haemolysis.
What is the epidemiology of Sickle cell anaemia?
The prevalence of sickle cell trait in sub-Saharan Africa is the highest in the world. This may be because it is protective against malaria.
RFs of Sickle cell
- African: 8% of black people carry the sickle cell gene
- Family history: autosomal recessive pattern
- Triggers of sickling: dehydration, acidosis, infection, and hypoxia
What is sickle cell caused by
defective haemoglobin. Specifically, the β-globin chains end up misshapen. This is because of a mutation in the beta globin gene, or HBB gene.
1 gene mutation - sickle cell trait - if both mutated sickle cell dissease
What happens due to the abnormal beta chain in SCA?
Sickle trait - reduced levels of HbA
Sickle disease - Absent HbA - has HbS - 2 A and 2 abnormal B chains - prone to siclking and haemolyss
HbS and oxygen
Carries it well
When deoxygenated changes shape allowing it to aggregate with other HbS proteins forming long polymers distorting RBC into crescent shape - Sickling
What is sickling triggered by
dehydration, acidosis, infection, and hypoxia. HbAS(trait) patients sickle at PaO22.5 - 4 kPa, whilstHbSS(disease) patients at PaO25 - 6 kPa.
What does repeated sickling promote
Damages cell membrane - promotes premature destruction - haemolysis - leads to anaemia + free haemoglobin
What happens with free haemoglobin
Free haemoglobin in plasma bound by haptoglobin and gets recycled
Recycling of that heme group yields unconjugated bilirubin, which at high concentration can cause scleral icterus, jaundice, and gallstones.
BM + SCA
To counteract the anaemia of sickle cell disease, the bone marrow makes increased numbers of reticulocytes. This can cause the bones to enlarge
Splenomegaly also happens
RBCs get stuck in capillaries causing vaso occlusion in sickled form - what can this lead to?
dactylitis, priapism, acute chest syndrome, stroke, depending on where the occlusion is
S + S of SCA
Pain
Anaemia symptoms
Jaundice
Sequestrastion, aplastic, haemolytic and vaso-occlusive crisis
Primary investigations for SCA
Newborn screening
FBC
Bloodfilm
Hb electrophoresis + solubility
Acute management of Anaemia
Analgesia
Hydration
Oxygen
Antibiotics
Blood transfusion
Chronic management of Sickle cell
Pain management
Hydroxycarbamide - increases level of HbF
Lifelong phenoxymethylpenicillin
Vaccinations
Blood transfusion
BM transpant
