Chronic Childhood Disease In Acute Setting

Question 1

Red blood cells

Answer 1

Enucleated biconcave discs

Last approx 120days

Large surface area volume

Stackable

Deformable and so can fit through tiny capillaries

Transport oxygen and carbon dioxide and act as a buffer to H+

Question 2

Haemoglobin

Answer 2

Each erythrocyte contains 280000000 haemoglobin molecules

Adult Hb molecules are made up of four globin chains, which consist of two alpha chains and two beta chains

Hb has four iron constraining heme units, one located within each globin chain

The iron molecule in the gene unit is required for oxygen transportation

Question 3

Haemoglobin molecule

Answer 3

Alpha chain

Beta chain

Question 4

Red blood cell production

Answer 4

Red blood cell number, eg haemorrhage, results in hypoxia

O2 sensitive renal cells

Erythropoietin

Red bone marrow: stem cells mature faster

More circulating erythrocytes

Question 5

Haemoglobin genetics

Answer 5

Chromosomes 16 - alpha globin chain locus

Chromosomes 11- beta globin chain locus

Normal genetic sequence ensures correct sequence of amino acids in primary structure of the globin chains

Structure is essential for the effective function of haemoglobin

Question 6

Changing Hb type over 1st year

Answer 6

After birth the regulation of Hb changes from predominantly foetal Hb to adult Hb

At birth 80% Hb f

Between 6&12 months 97% Hb

Question 7

The haemoglobinopathies

Answer 7

Disorders of the red blood cells and

Haemoglobin include

Abnormal haemoglobin affecting red blood cell shape - sickle cell disease

Reduced or absent production of adult haemoglobin - thalassaemias

Question 8

Sickle cell disease

Answer 8

Autosomal recessive disorder: two copies of the sickle cell gene

All haemoglobin is of the HbSS sickle cell variety

hbss crystllises when the oxygen content of the blood is low resulting in the red blood cells becoming sickle shaped

Question 9

Sickle cell disease

Answer 9

The sickle mutation is a point mutation resulting in substitution of hydrophilic glutamic acid for hydrophobic valine in the b globin

12,500 to 15,000 people in the uk have sickle cell disease and this is increasing - affecting mainly but not exclusively people with a heritage back to areas of Africa

Sickle cell disease is now the most commonly inherited disease in England

Being sickle cell trait protects agains malaria -

Question 10

SCD pathology

Answer 10

Polymerisation of Hb molecules in RBC cause the formation of rigid tubular spiral divers which deform the rbc which forms a sickle shape

These sickle cells have a reduced life span, are not flexible like normal RBC and can get trapped in the micro circulation causing thrombosis and ischaemia in organs or bones

Question 11

Sickles cells

Answer 11

Breakdown of red blood cells

Clumping of cells and clogging of small blood vessels

Accumulation of sickles cells in spleen

Physical weakness 
Anemia 
HeR failure 
Pain and fever
Brain damage 
Damage to other organs 
Spleen damage 

Impaired metal function 
Paralysis 
Pneumonia and other infections 
Rhenumatism 
Kidney failure

Question 12

Acute complications

Answer 12

Vado-occlusive painful crisis

Dactylitis

RBC aplastic crisis

Acute chest syndrome

Cerhrovascular accident

Acute splenic sequestration

Priapism

Question 13

Chronic complications

Answer 13

Short stature and delayed puberty

Renal impairment

Usual impairment

Neurological impairment

Heart failure

Pigment gallstone ms

Leg ulcers

Question 14

Therapeutic strategies

Answer 14

Antenatal screening for early detection and education

Comprehensive, easy access, supportive services

Avoid precipitating factors

• optimal hydration
• prophylactic antibiotics
• standard immunisation, plus pneumococcal and flu

Low threshold for seeking help and early diagnosis of complications

Effective analgesia in acute painful episodes

Optimise haemoglobin level: exchange transfusions, hydroxyurea therapy

Trans cranial Doppler scanning

Question 15

Thalassaemia

Answer 15

A quantitative haemoglobin disorder

Autosomal recessive disease caused by multiple deletions of globin gens

Question 16

Thalassaemias

Answer 16

Produce either no or too little haemoglobin

A thalassaemia not enough alpha chain produced most common in Asian population

B thalassaemia not enough beta chain produced, most common in southern Italy and Greece

Thalassaemia trait or thalassaemia carrier no serious health problems themselves risk of having children with the condition

Question 17

Therapeutic strategies

Answer 17

Depending on the severity of the anaemia

4-6 weekly blood transfusions with 2-3 units aiming to maintain Hb at 10-12 g/dl

Desferrioxamine therapy - chelation of iron to prevent iron toxicity

Hydroxyurea

Stem cell or bone marrow transplants are the only cure for thalassaemia not done very often because of the significant risk involved

Question 18

Summary

Answer 18

Haemoglobinopathies have a significant impact on health and quality of life

They are heritable disease and so can be seen in multiple members of the same family

Early diagnosis, education, surveillance and prevention are all important

Early intervention when health problems arise is key

Question 19

What is CF

Answer 19

CF is a multi-system disorderly, characterised by chronic airway obstruction and infection and pancreatic insufficiency

The root cause is a single gene mutation affecting a chloride channel protein in exocrine glands

This channel primarily regulates the passage of chloride across the luminal cell membranes with secondary effects on sodium and water transport

The net effec is of a thickening of exocrine gland secretions throughout the respiratory and alimentary tracts, sweat ducts and the reproductive organs