Transcript Coeliac Disease Renal failure

Bruno Sopko
Tomáš Kučera
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Gluten peptides must be able to reach the gut
epithelium
once in the epithelium, they are (in part) deamidated by
tissue type transglutaminase
conversion of glutamine into glutamic acid is crucial in
the toxic mechanism
Deamidated peptides of gliadin or glutenin are able to
bind to an antigen presenting cell
This cell presents the antigen to a CD4 T-cell, which
becomes activated and produces signals that activate
both plasma cells (production of IgA-type antibodies
and anti-tTG-antibodies) and lymphocytes
Activation of T-cells is thought to start a cascade of
reactions that lead to damage of the intestinal
epithelium.
The finger shaped villi of the intestine are lost and the
capacity to absorb nutrients is dramatically reduced
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Patient (female) was a healthy baby who grew normally until 12
months old, when her parents noticed that she became irritable
and stopped gaining weight. She was observed closely by her
paediatrician for the next 3 months during which time she
developed a distended abdomen, passed large, foul-smelling
stools, and lost nearly 2 kg in weight. Her parents also noticed
that the patient was becoming progressively weaker.
At birth, patient weighed 3.8 kg, was 52 cm long, and had a
head circumference of 36 cm (all within the normal range). She
grew normally until nearly 15 months of age and reached all the
developmental milestones appropriately.
Both of her parents were healthy, as was her 3-year-old sister.
There was no known history of metabolic, neurologic, or
gastrointestinal disease in children in the family. There was no
history of autoimmune diseases, including type 1 diabetes
mellitus.
Referred to children hospital at 15
months. When she arrived she
appeared pale and chronically ill. She
weighed 8.5 kg (5th centile), her
height was 77.5 cm (50th centile), and
her head circumference was 46 cm
(50th centile). The examination made
patient fretful but she could be
consoled. She was mildly dehydrated,
and had a protuberant abdomen and
significant muscle wasting in her
buttocks, legs, and arms (Case Figure
44.1). No enlargement of liver, spleen,
or lymph nodes was evident.
Laboratory tests:
 anemia, with a hemoglobin level of 10 g dl−1 (normal 12–14 g dl−1).
 white-cell count and platelets were normal.
 mild elevation of liver enzymes (transaminitis), with aspartate
aminotransferase at 48 U l−1 (normal range 2–40 U l−1) and alanine
aminotransferase at 46 U l−1 (normal range 3–30 U l−1).
 albumin was normal at 3.7 g dl−1.
 No evidence of metabolic disease was found, and so serologic samples
for testing for celiac disease were sent to the laboratory.
 tested positive for anti-endomysium IgA antibodies (autoantibodies
against the connective tissue that sheathes muscle—the endomysium) at
a titer of 1:2560 and for anti-tissue transglutaminase (TTG) IgA
antibodies at a level greater than 118 U ml−1 (greater than 25 U ml−1 is
considered positive).
 positive for anti-gliadin IgA antibodies at greater than 104 U ml−1
(greater than 23 U ml−1 is considered positive) and anti-gliadin IgG
antibodies at greater than 77 U ml−1 (greater than 28 U ml−1 is
considered positive).
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What is the cause of malnutrition in case of
Coeliac Disease?
Why has patient been dehydrated?
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76-year-old woman for the first time at a local nursing home. Her
medical history includes iron deficiency anemia, osteopenia, and
hypothyroidism. Her only surgery was a hysterectomy for uterine
fibroids 30 years earlier. She takes iron supplements, a bisphosphonate,
and thyroid hormone replacement therapy. She feels generally well,
although she reports fatigue and decreased energy. Her weight has been
stable, and she is active in her nursing home community. A review of
systems is otherwise negative, and physical findings are unremarkable.
A previous workup for iron deficiency revealed no GI source of bleeding.
Multiple fecal occult blood tests were negative, and the results of 2
colonoscopies and upper endoscopies were normal. There are no other
apparent sources of blood loss; she had a hysterectomy years earlier,
and her urine has never contained gross or microscopic blood.
Despite the patient's adherence to the iron replacement regimen,
laboratory values continue to be abnormal (hemoglobin, 10.4 g/dL; red
blood cell distribution width, 20%; mean corpuscular volume, 70 μm3;
and ferritin, 20 ng/mL. Iron deficiency is limiting her quality of life.
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A gluten-free diet was prescribed. The
patient's ferritin level increased, and the
anemia and microcytosis resolved. She also
reported increased energy.
Why gluten-free diet helped?
Could celiac disease have contributed to her
osteopenia and hypothyroidism as well.
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A 30-year-old woman was admitted with a 4-week history of increasing
bloody diarrhoea and abdominal pain; she had lost 3kg in weight. She
smoked 25 cigarettes a day. On examination, she was not clinically anaemic
and, apart from a temperature of 37.8°C and some tenderness over the
right iliac fossa, there were no abnormal physical signs. The perineum was
normal but sigmoidoscopy to 15cm showed a red, granular mucosa with
mucopus and contact bleeding. Laboratory investigations showed a low
haemoglobin (108g/l) with a raised CRP (67 mg/l) but a normal white-cell
count. Urea and electrolytes, serum vitamin B12, folate, iron, ferritin and
iron-binding capacity were normal. Her total serum proteins were 54g/l (NR
62-82) with a serum albumin of 29g/l (NR 35-50). Antibodies to neutrophil
cytoplasmic antigens (ANCA) were not detected. Faecal examination and
culture revealed no ova or Campylobacter. Clostridium difficile toxin was
absent from the stools.
The rectal biopsy taken at sigmoidoscopy showed a small area of ulceration
of the surface epithelium with considerable mucopus. Many crypt abscesses
were present. The lamina propria contained a heavy infiltrate of
lymphocytes, plasma cells and macrophages. Two non-caseating
granulomas were present
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The appearances were those of Crohn's
disease affecting the colon. A small-bowel
barium infusion and a colonoscopy were
performed to assess the extent of disease.
Inflammatory strictures were seen at a
number of separate sites (skip lesions) in the
ascending and transverse colons. She was
treated with corticosteroids and a 3-month
course of metronidazole with symptomatic
improvement. She was strongly advised to
stop smoking.
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Renal failure (also kidney failure or renal insufficiency) is a medical
condition in which the kidneys fail to adequately filter waste products
from the blood. The two main forms are acute kidney injury, which is
often reversible with adequate treatment, and chronic kidney disease,
which is often not reversible. In both cases, there is usually an
underlying cause.
Renal failure is mainly determined by a decrease in glomerular filtration
rate, the rate at which blood is filtered in the glomeruli of the kidney.
This is detected by a decrease in or absence of urine production or
determination of waste products (creatinine or urea) in the blood.
Depending on the cause, haematuria (blood loss in the urine) and
proteinuria (protein loss in the urine) may be noted.
In renal failure, there may be problems with increased fluid in the body
(leading to swelling), increased acid levels, raised levels of potassium,
decreased levels of calcium, increased levels of phosphate, and in later
stages anemia. Bone health may also be affected. Long-term kidney
problems are associated with an increased risk of cardiovascular
disease.
Chemistry
The patient is a 41 year-old male who has a longstanding
history of hypertension and diabetes and presents with a
complaint of pruritis, lethargy, lower extremity edema,
nausea and emesis. He denies any other medical illnesses.
On physical exam the patient is a well-developed, wellnourished male in moderate distress. Blood pressure
180/110, pulse 80, respirations 24 and he was afebrile.
Body weight 76.5 kg. HEENT was remarkable for
fundoscopic findings of A-V nicking and copper wire
changes consistent with hypertensive injury. Cardiac exam
had an S1, S2 and S4. The remainder of the exam was
remarkable for 2+ lower extremity edema and superficial
excoriations of his skin from scratching.
Laboratory Data
24-hour urine protein and creatinine - volume 850 ml,
protein 600 mg/dl and creatinine 180 mg/dl
Renal ultrasound- Right kidney 9 x 6.0 cm, Left kidney 9.2 x
5.8 cm
Both kidneys illustrate hyperechogenicity and no
hydronephrosis.
Normal Values
Sodium
133
136-146
mmol/L
Potassium
6.2
3.5-5.3
mmol/L
Chloride
100
98-108
mmol/L
Total CO2
15
23-27 mmol/L
BUN
170
7-22 mg/dl
Creatinine
Glucose
16.0
0.7-1.5 mg/dl
108
70-110 mg/dl
Calcium
7.2
8.9-10.3
mg/dl
Phosphorus
10.5
2.6-6.4 mg/dl
Alkaline
Phosphatase 306
Parathyroid
Hormone
Hemoglobin
Hematocrit
Mean
cell
volume
30-110 IU/L
895
10-65 pg/ml
8.6
14-17 gm/dl
27.4
40-54 %
88
85-95 FL
Urinalysis
pH 6.0
Specific
gravity
1.010
Protein 1+
Glucose
negative
Acetone
negative
Occult
blood
negative
Bile
negative
Waxy
casts
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Is the cause of this patient’s renal failure
acute or chronic? How did you arrive at that
conclusion?
What is the measured GFR in this patient?
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Patient, female, age 45, was admitted to the emergency room following
a major automobile accident in which her husband was killed. She had
massive abdominal injuries and a fractured femur. She was taken
immediately to surgery for repair of a lacerated liver and perforated
ileum. She had two units of blood during surgery and two units while
she was in the recovery room. The fifth unit of blood was discontinued
in surgical intensive care because she developed a transfusion reaction.
On the day after surgery, her urine output declined to 10-20 ml/hr.
Increasing her fluid intake with plasma expanders and blood did not
increase her urine output. Lab results indicated an elevated urinary
sodium, BUN 70 mg/dl, and serum creatinine 4 mg/dl.
Her urine output stabilized at 20-25 ml/hr on the third day after
surgery. She was diagnosed as having acute tubular necrosis.
Because of a persistently elevated serum potassium and severe
hypertension (BP 190/120), she was started on hemodialysis using an
external cannula.
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Is the cause of this patient’s renal failure
acute or chronic? How did you arrive at that
conclusion?
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Patient, male, age 8 year.
Reasons for visiting GP: Oedema, dyspnoea, haematuria.
Family history: Father, mother and younger brother - healthy.
Personal medical history: Delivery normal, standard development, no serious
illness.
Present medical history: 2 weeks ago suffered from fever - 38,5°C, sore throat ,
tonsillitis. Stayed in bed, acetaminophen, in 3 days fever back to normal, in one
week feeling well. Yesterday, observed dark urine. Today morning facial oedema
and swollen legs, vomiting in the morning, pain in the abdomen and in the lumbar
region, decreased urination. Visited GP, detected haematuria, then referred to
children hospital.
Patient feels tired, inappetence, no fever. Complained about dyspnoea.
Observation: BP 150/95 pulse 110/min T 36,5°C.
Tired, dyspnoea, facial oedema (with eye lids), pale. Lungs without pathological
observation. Abdomen without any pathological observation, only increased
sensitiveness. Symmetrical oeademas of both lower extremities .
Laboratory exam.: FW 60/90. Diuresis: 300ml/24h . Urine: acidic, high osmolality,
blood +++ protein ++ . Urine sediment: erythrocytes, erythrocytal cylinders. In
serum: Na 133 mmol/l K 5,8 mmol/l urea 15 mmol/l creatinine 180 umol/l CRP
45 mg/l albumin 28 g/l . Normal Cl, glukose, ALT, AST, ALP, GMT, bilirubin
normal. Blood – pH 7,29 pCO2 4,5 HCO3 17,0 BE -5,2 . KO: Leu 8,0 Hb 115 . IgG
increased , ASLO: positive.
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What is the probable illness? Diagnose or characterise the disease.
Acute post-streptococcus glomerulonephritis, observed with two week latency
after tonsillitis ( one of the so called sterile or post-streptococcus consequences.
Together with rheumatic fever and chorea minor).
What is the mechanism of oedema formation?
Acute renal failure with oliguria, adn water and salt retention. The failure is
the consequence of the production of antibodies against the structures of Str.
pyogenes (probable source of the infection 2 weeks ago). These antibodies react
also with the basal glomerulal membrane.
What are the symptoms causes by increased sosium and water content in the
organism?
dyspnoea (blood in lungs), increased intravascular liquid volume (kidneys’
excretion limited → liquids are remaining in the veins → blood congestion).
Oedemas of lower extremities, face and eyelids (typical for renal failure…rare
occurrence of anasarca).
Anasarca- complete, whole body oedema (“soaked” organism)
What, non-pharmacological, treatment will be apllied?
Correction of water and electrolyte uptake.