Presentation Transcript

1. Coeliac DiseaseRenal failure

   Bruno Sopko Tomáš Kučera
2. Coeliac Disease 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 crucialin the toxic mechanism Deamidated peptides of gliadin orglutenin are able to bind to an antigen presenting cell This cell presents theantigen to a CD4 T-cell, which becomes activated and produces signals that activate bothplasma 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 damageof the intestinal epithelium. The finger shaped villi of the intestine are lost andthe capacity to absorb nutrients is dramatically reduced
3. Coeliac Disease
4. Case study 1 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.
5. Case study 1 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.
6. Case study 1 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).
7. Case study 1 What is the cause of malnutrition in case of Coeliac Disease? Why has patient been dehydrated?
8. Case study 2 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.
9. Case study 2 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? Couldceliac disease have contributed to her osteopenia and hypothyroidism as well.
10. Case study 3 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 neutrophilcytoplasmic 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-caseatinggranulomas were present
11. Case study 3
12. Case study 3 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.
13. Renal failure 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.
14. Case study 1 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, well-nourished 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/dlRenal ultrasound- Right kidney 9 x 6.0 cm, Left kidney 9.2 x 5.8 cmBoth kidneys illustrate hyperechogenicity and no hydronephrosis.
15. Case study 1 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?
16. Case study 2 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.
17. Case study 2 Is the cause of this patient’s renal failure acute or chronic? How did you arrive at that conclusion?
18. Case study 3 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.
19. Case study 3 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.