Minutes
Astro Boy
Trigger 1:
Tim
ED:
4.5/12
2/52 h/o grad ↑ SOB on min exertion – eg”sucking”
DIMTOP
D:
I:
M
T:
O:
P:
lead poisoning, breast milk,
Allergies, asthma (normally not Dx before 2yoa), RTI, TB (chr inf of lungs – forms
“tubercles” - mycobacterial)
Acidosis,
Leukaemia (marrow - ↑WBC so ↓RBC →anaemia),
Congenital heart disease, ?anaemia (?congenital, aplastic) RTI’s (viral or bacterial?,
is this first episode?),
Battery,
Questions to ask
Household Changes, Mum’s medication, sleeping patterns, siblings/ family history,
?development – weight centiles (?staying on desired / birth centile), birth weight. ? prem birth
– lungs in pre-term baby = ↓ surfactant. ? first pregnancy, ? birth complications eg
preeclampsia = nutritional deficit,
Hypothesis:
?Acute / Chronic:
2/52, ? had before.
? Cystic fibrosis, ? emotile cilial syndrome → dysfunction
? Shaken baby syndrome→chest xray, skull fractures
Info found:
CHD: atrio – vent septal defect. “hole in heart” = most common defect. ↑SOB, blood mixing
in chambers, ↓O2. Failure to thrive.
Metabolic Acidosis: Renal failure may be contributing. Normal kidney function has an
important role in acid homeostasis. The kidneys are responsible for reabsorption of filtered
bicarbonate ions through the mechanism for H+ secretion. It can present with ‘kussmaul
respiration’ – attempt to remove CO2 from the body.
Disorders relating to food metabolism → SOB = disturbs pH, metab acidosis→ compensate
by ↑ esp rate to blow off Co2/H+.
Trigg 2
Ti youngest of 3 (not refugee or from “exposed” country)
10 y/o sister 8 y/o brother
Dad commercial lawyer, Mum p/t accountant. (parent literacy)
Birth normal 3.5kg, APGAR score = 10
Despite initially well, nasal discharge since birth.
Poor WG despite good appetite for breast milk
10/52 = URTI → bronchitis, responded to Ab. Otitis media ( middle ear inf) shortly after →
again responded well to Ab.
Ear inf 2/52 later, again Ab successful.
6/52→ 20+ times per day diaorrhea
5 hosp admissions since born. Most recent 3/52 ago treated with IV fluids.
APGAR:
Colour
Breathing
HR
M tone
Response to touch
Questions to ask
? immune system compromised / effected
Leukaemia
Acidosis kidneys
Acquired Immune deficiency
Anaemia congenital
Resp Inf – in immune compromised
Found Out:
Hannah is a Rabbit
Leukaemia: asscoc with diaorrhea. 2 types Lymph/myo blastic cells. Age 2-5 most
common = Acute Lymphoblastic Leuk Fever - (inf) WL, bruising (↓platelet count)
Acidosis kidneys:
Can involve diabetes, poisons, kidney disease. Can get diaorrhea as a
result. Resp distress = comp mechanism. May exp why Tim had IV fluids. Does not correlate
with no. of infections Tim has had (4-8 in first year of life OK)
Acquired Immune deficiency: Dev due to non genetic abnormalities. Acquired during life.
HIV (Human Immuno-deficiency Virus) = most common. Affects T-Lymphocytes – innate
immunity. Drops count of T-lymphocytes. Other factors = nutritional (albumin paucity due to
↓ protein effects synthesis), medical treatments, infections.
Anaemia congenital: Caused by congen defects leading to cell production and maturation
defect. Many types of deficiency Common factor = inf comp↑susceptability to inf manifested
after birth.
Respiratory Inf – in immune-compromised: Often present with recurrent symptoms. Eg
epsteint barr virus→ damage leads to compromised defence system in patient. Considered”
likely” in Tim’s case. Middle cear com site – it is more the freq that concerns us
Types of Immunity. Work differently:
Cell Mediated Immunity T- Lymphocytes – manifests first few months of life.
Humoral Immunity M– more of an issue in last half of first of year as still getting
mum’s immunity before then. (Think timing of “booster” shots)
Adaptive Immunity: Specific lymphocytes: B cells → humoral (marrow), T Cells
(Thymus)→cell mediated. Heve “memory” for subseq inf.
Innate: (Non-specific) neutrophils/ macrophages
Trigger 3
Examination:
Obs: Irritable / cyanosed infant. (lips, tongue)
RR 40/min
BP 85/55
HR 160/min
T 37.8
W 3.6kg (< ist cent), muscle wasting noted
White plaques on tongeue
Buccal mucosa
Mucopurulent d/charge from nose
No visible tonsillar tissue
Ausc: audible wheeze, with widespread crackles over liung fies. I/C recession and trach tug.
Ear: Tymp Memb (separates middle from inner ear – t’mits sound) bilat inflamed
Abdo: Exam difficult - passed 50mls faeces during
No signs chronic liver disease.
Genital rash extending to anus. Excoriated, raised, red
I/C admission
Samples taken for inv:→ blood, faeces, urine, mouth swab, chest x-Ray, (mucus→gastric
washings in kids).
Need to know:
Resp: Nasal Discharge. Mucopurulent = mucus AND pus
Resp: Auscultation Crackles –(explosive sounds in airway. Fluid related“ like crumpling
up chip packet”. Trach tug downward movement of hr cart. Aortic aneurism, COPD,
Intercostal Recession→ negative intrathoracic pressure causing indrawing
Vitals: RR 40 (30 -45)
HR 160 (90-120)
T 37.8 (36.5-37.5)
Wt 3.6kg 1st cent < (7kg)
BP 85/55
Abdo / GIT
Genital Rash:
“nappy rash” skin exp to wet dirty nappies. Thrush or other fungal
infection can also cause. Often worse in immune-compromised babies.
Birth weight / Development:
Muscle Wasting:
Secondary to failure to thrive
Yellow Stool:
Sign of GIT infection (can be white also)
Pallatine tonsil:
First line of pathogen defence. Lymphoid tissue. Can be eroded by acid
reflux.
Found Out:
Resp: Nasal Discharge
Resp: Auscultation: wheeze and crackles due to mucus buid-up
Abdo / GIT
Genital Rash
Birth weight / Development:
Muscle Wasting:
Buccal mucosa
Session 2:
Summary of above presented.
So: multiple organ involvement. Widespread infection. WHY?
Probably an immunity problem
Trigger 4
Investigations:
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Radiology: Bilateral diffuse opacities in both lung fields in an interstitial pattern. The
Radiologist commented that the pattern of interstitial pneumonitis was consistent with
Pneumocystitis carinii.
No Thymic shadow seen on film
Faecal exam: no parasite seen
latex agglutination for Rotavirus - positive → ? causing diarrhoea
Oral, Groin scrapings: Candida albicans
Neutrophil Respiratory Burst Test: 95% (N=> 90)
Electron Microscopy of cilia = normal
Nasopharyngeal aspirate - Gram neg bacilli on gram stain, culture grew pseudomonas
aeruginosa.
DNA test for cystic fibrosis: negative
HIV antibody: negative.
Serum biochemistry and blood gases: were consistent with severe dehydration and
respiratory failure requiring mechanical ventilation
Found Out:
Pseudomonas aeruginosa:
gram neg bacilli. Bacterial commensal.
Commensal = usually normal flora, but can be infective if
immune system deficient.
Aerobic. Lungs. Few nutritional requirements.
Significance: presence in lower resp tract = indicative of
immune deficiency.
Nutritional Burst Test
oxidative burst, O2 dep method of killing bacteria. Less chem
in cell very active. Tests for partic aspect of immune system.
Tests for ability of body to be able to kill and phagocytose
bacteria. Seems to be intact given normal radings. If was low,
may indicate secondary problem
PCP
Fungus. Common in environment / air. Not normally in lung.
Presence = immune deficiency
Should appear as relatively large in infants / children. If not
visible will affect immunity→ T cell compromise (mature in
Thymus), ↓ adaptive response capacity.
Thymic shadow
Trigger: 5
Investigations (cont)
Haeamatology:
Hb
80.0 (100-140g/l) Low
WCC
4.8 (4.0-11.0) x109 Lower end of Normal
Lymphocytes 0.76 (2.2-7.0)* x109 Low
*may vary from one lab to another but note that is higher than in adults (this comment
from “Gordo’s Notes”)
Immunoglobulins:
IgG 1.7 (1.7-8.1) g/l
Low end of Normal
IgA <0.01 (0.04-0.84) g/l Very Low
IgM <0.01 (0.27-1.0) g/l Very Low
(age adjusted reference ranges allow for lowest to highest concentrations from 4-5 months of
age)
Lymphocyte subsets
CD3 <0.01 (1.7-3.6) x 109 (all T Cells)
Very Low
9
CD4 <0.01 (1.7-2.8) x 10 (helper-induced cells) Very Low
CD8 <0.01 (0.8-1.2) x 109 (cytotoxic suppressor cells) Very Low
CD19 0.75 (0.5-1.5) x 109 (all B Cells)
Normal
9
CD16 0.07 (0.3-0.7) x 10 (Natural killer cells)
Very Low
Complement concentration and activity
C3
1.6 (0.9-1.8) g/l Normal
C4
0.31 (0.16-0.50) g/l Normal
CH50 578 (520-660) U/ml RI is method dependant
Summary
Low Hb
Lacks Thymus: Therefore unable to make functional T cells (maturation dysfunction). T cell
abnormalities in keeping with thymal deficit.
Immature CD4 and CD8 cells are matured in the Thymus → CD4+ and
CD8+.
T Cells: In thymus→pos and negative selection. Dendritic interaction
All nucleated cells have potential to present MHC on membrane which can
be potentially targeted by T cells → apoptosis.
See Link:
http://www.youtube.com/watch?v=odLLr6mjaUQ
Cytokines are necessary
Tim’s B cells are normal but because fo the lack of Helper T cells, they are unable to undergo
clonal expansion despite his infections → low immunoglobulin
Lack of T Helper cells also means the NK cells (part of INNATE ) immunity are not
activated either despite his frequent infections
IgG
Borderline (may have maternal IgG)
IgA, IgM both low: Tim’s dysfunction
Lack of latter two = B Cell dysfunction. Immunoglobulins not being produced adequately.
Relevance: B cell numbers Ok, but not functioning well.
Lymphocytes: Low numbers = adaptive response compromised
Compliment concentration and activity:
Involved in innate and adaptive component.
Normal readings → intact
So: Not HIV positive
Trigger 6
Tim’s results were consistent with Severe Combined Immunodeficiency Disease (SCID)
Tim required mechanical ventilation and treatment with multiple intravenous antibiotics and
a tropical antifungal. Intravenous feeding was instituted in an effort to improve his nutrition.
He was transfused with a unit of fresh, irradiated cross-matched CMV-negative whole blood
followed by subcutaneous immunoglobulin daily for four days. He made slow but steady
progress on this regimen and came off the ventilator after seven days.
Siblings and parents were HLA typed
So:
Given irradiated blood:
Don’t want T and B cell from donor blood attacking the host.
Gamma rays are used to destroy lymphocytes. Limit graft v host response.
In normal – host lymphocytes would normally kill donor lymphocytes
Bone Marrow Transplant – beware graft v host response
IV feeding: Malabsorption through GIT.
If IGa deficient will also negatively impact in GIT
HLA important for transplants.
Irradiate to eliminate pathogens
Cross matching to limit chance of blood attacking self
Limit chance of reactions given limited defence.
SCID:
Causes:
genetic syndrome
↓ T cells, failure to thrive, chronic diarrhoea
50% = x-linked.
Autosomal recessive = remainder ( ¼ affected, 2 in 4 = carriers)
See Link for SCID
http://www.scid.net/
See Link below for X-Linked explanation
http://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency
Trigger:7
Tim continued to respond well to treatment
Bone marrow transplant at one month following admission once well enough to undergo
operation.His 10y/o sister was found to have the closest match in HLA antigens. Mum
expressed concern re donations, offered to make donations herself.
So:
Mother can only have 50% match
Siblings more likely to have a better match?
Obvious issues of donations by minors – see relevant learning objective.(14.10)
Rejection an issue. Graft v Host response.
Why particularly significant with immune deficiency.
On anti rejection drugs long term
Last trigger:
Closure:
3/52 post transplant, definite evidence of engraftment based on the rising lymphocyte count.
3/12 post transplant, there was complete engraftment so that all immunology tests returned to
normal.
10th centile for height and weight. (prev 1st)
So:
Which parts of immune system addressed by transplan? Every blood cell type would have
potential to be addressed. Reconstituting immunity system via “production-line” effect.
Transfused Ig products by contrast have a “shelf life”.
Note: Thymus part of reticuloendotheleial system.