1 semester II

Question 1

1. A 60 year-old man complains of weight loss, diarrhea alternating with constipation. The patient is pale (anemic). What tests would you perform?

Answer 1

• Weight loss, diarrhea/constipation + anemia in pt of this age → GI malignancy
  
  • Other possibilities for weight loss in elderly include depression , but with these GIsymptoms, tumor is likely
• Alternating constipation + diarrhea due to obstruction via tumor → formation of large, dry stoolmass → osmotic activity of mass eventually draws a lot of water from bowel → diarrhea
• Can perform an occult blood test - aka “hemoccult” test, recommended as yearly GI cancerscreening for pts above 45
• Can also check GI tumor markers :
  
  • CEA (carcinoembryonic antigen) - not specific, but often elevated incolorectal/gastric/pancreatic and other carcinomas
  • CA 19-9 (carbohydrate antigen) - AKA Sialyl-Lewis A, elevated in colon/pancreaticcancers
• Check hematocrit for the anemia: tumor may bleed directly or consume RBC co-factors
• Perform endoscopy and colonoscopy.
• Irrigoscopy - patient drinks contrast agent + GI tract is visualized; area where contrast not seenmay be tumor
• Can do various imaging studies (MRI, CT, etc.) for metastases

(**Colon cancer constipation alternating diarrhea is due to blockage in the GI, build up of . .. + bacteria will digest and thats why diarrhea.Check for blood in … Colonoscopy - to see the inside, if suspecting in the microscopy, biopsy is takenCT examination gives s good idea but no biopsy can be taken.**)

Question 2

2. A patient with symptoms of chronic alcoholism complains of recurrent abdominal pain, meteorism. He has lost weight in the past few months, his stools are voluminous, difficult to flush.

serum Ca: 2.1 mmol/l

prothrombin time INR: 2.6; normalized after vitamin K administration

serum glucose (fasting): 12 mmol/l

ALP: 264 U/l

albumin: 40 g/l

fecal elastase: decreasedabdominal

ultrasound: enlarged pancreas

What is your diagnosis? What other tests would you do?

Answer 2

• “Meteorism” (bloating) and big, difficult to flush stool → issues digesting fat → steatorrhea
• Slightly low serum Ca⁺⁺ (<2.2 mmol/l) via two mechanisms:
  
  • decreased vitamin D absorption via fat malabsorption
  • “saponification” of FFAs with Ca ++ in the damaged pancreas
• Prothrombin time elongated (>1.2 INR) fixed by vit. K → fat/vit. k malabsorption
• Very high fasting glucose (>7 mmol/l) → decreased insulin production
• High ALP (>150 U/l) → bone resorption to accommodate ↓ Ca ++
  
  • Hamar: ALP increase here is mild, so obstruction is not the likely cause of pancreatitis.
• Normal albumin (35-50 g/l) → inflammation is not acute
• Fecal elastase decrease → decreased pancreatic exocrine activity
  
  • Elastase is synthesized equimolar with other pancreatic enzymes + its level in fecesindicates exocrine activity (decrease indicates chronic pancreatitis)
• Enlarged pancreas on US → pancreatitis
• Probably chronic pancreatitis because of normal albumin (would be lowered in acute phase rxn).
  
  • Main cause of this is alcoholism , but may also be autoimmune.
• Need to rule out pancreatic cancer so must perform endoscopic retrogradecholecysto-pancreatography (ERCP).

(**meteorism - a lot …Chronic pancreatitisLack of lipase - lipid digestion -> Mal absorption of lipids -> Mal absorption of vit KDiabetes may develop ..Elastase - produced in the pancreas (many others are digested)Ca++. a bit lower - vit K is lower, we can assume that Vit D is also low (bone…)IV secretin - chole… than sucking the produced pancreatic juice (disadvantage - tube is needed)Pancreolauryl test**)

Question 3

3. A patient complains of intense periumbilical pain of sudden onset. His blood pressure is low, the pulse is fast, he is sweating and has nausea. There is no defense on physical examination of the abdomen.

Laboratory results:

• ESR: 42 mm/h
• WBC: 11 G/l
• serum α-amylase: 1800 U/l
• urine α-amylase: increased
• serum lipase: increased
• serum urea: 10 mmol/l
• serum creatinine: 90 μmol/l
• serum Ca: 1.9 mmol/l
• serum albumin: 30 g/l
• fasting blood glucose: 6.5 mmol/l.

What is your diagnosis? What other tests would you perform?

Answer 3

• High ESR (>20 mm/h) → inflammation
  
  • In inflammation, increased serum fibrinogen causes RBCs to stick together and form“rouleaux” which settle faster via increased density.
• High WBC (>10 G/l) indicates inflammation / immune reaction
• High α-amylase (>180 U/l), urine amylase and serum lipase indicates pancreatitis
• Serum urea is borderline high → slightly impaired kidney function○ can be via redistribution of blood flow in early shock (low BP, high HR)
• Creatinine is normal (40-130 uM)
• Ca⁺⁺ is low (<2.2 mM) indicating impaired fat digestion → ↓ vitamin D○ In pancreatitis, autodigestion via lipase → “saponification” of FFAs + Ca → ↓ Ca⁺⁺ (elongated QT on ECG)
• Serum albumin is low (<35 g/l) indicating acute inflammation
• Fasting glucose is high (>6.0 mM) → low insulin secretion, but not actually…
  
  • ~90% islets must be destroyed before glucose ↑
  • in acute inflammation, stress hormone elevation → high gluconeogenesis
• Periumbilical or “belt-like” pain is typical of pancreatitis.
• Low BP + tachycardia point to the beginnings of shock.
  
  • Shock Index = HR / Systolic BP … should be around 0.5-0.66 … >1 indicates probableshock (means ↑ HR ↓ BP)
• This is acute pancreatitis , because of the high ESR, low albumin and high serum/urine pancreaticenzymes.
• Imaging studies (US, CT or MRI) can be done to confirm pancreatic enlargement
• Commonly caused by cholelithiasis or alcohol and greasy foods.
  
  • Alcohol dehydrates pancreatic secretions + need for more lipase to digest foods →viscous secretions back up in pancreatic ducts → autolysis + inflammation
• Treatment is symptomatic: NPO (“nil per os”, no food/drink by mouth) and painkillers

(**ESR: 42 mm/h. - suggesting inflammationWBC: 11 G/l - slightly elevatedserum α-amylase: 1800 U/l - highurine α-amylase: increasedserum lipase: increased*** acute pancreatitis (if lipase is not elevated the others could be a result of salivary glands)intense periumbilical pain of sudden onset - typical for acute pancreatitisserum urea: 10 mmol/l - slightly elevated (kidney failure due to shock)serum creatinine: 90 μmol/l serum Ca: 1.9 mmol/l (hypocalcemia - know the reason and the ECG sign)serum albumin: 30 g/l (low, maybe due to inflammatory reaction)fasting blood glucose: 6.5 mmol/l (any major inflammation/stress may cause)Acute pancreatitis.other tests: no need for further (amylase, lipase is enough)- other examinations are needed in order to check if the patient is getting better or worse (serum CRP - Everyday), which type of pancreatitis (adematus, necrotic) - imaging (US only size)(CT - will see necrotic area)**)

Question 4

4. A 35 year-old man complains of heartburn and occasional regurgitation of sour material in his mouth, mostly in the morning especially if leaning down. These symptoms were provoked by drinking beer the evening before. Findings of an esophago-gastro-duodenoscopy: the proxymal part of the esophagus is normal, but the distal part is hyperemic with erosions. The cardia is loose, the antrum is hyperemic in patches. The bulbus and the postbulbar duodenum is normal.

What is your diagnosis?

What further test and treatment should be considered?

Answer 4

• This is GERD (gastroesophageal reflux disease).
• Main causes are: LES insufficiency, diaphragmatic hernia, acid overproduction, obesity, 3rd trimester pregnancy
• Tests : diagnosis of GERD is usually made based on symptoms, but certain tests can be done if acase does not respond well to therapy, or prior to surgery
  
  • Esophageal manometry - done prior to surgery, a nasogastric catheter is lowered intothe stomach and then slowly withdrawn as it measures pressure changes
  • Endoscopy with biopsy - can culture a sample from ulcer to check for H. pylori
  • Urea Breath Test - to check for H. pylori
• Treatment :
  
  • If H. pylori positive → triple therapy : clarithromycin, amoxicillin and PPI○ Patient can avoid eating/drinking before lying down and avoid alcohol/coffee and spicyfood.
  • PPIs such as omeprazole can reduce gastric acidity

(**GEGDother tests: - H.pylori infection (Biopsy+culture)/(urea exhalation test)treatment - PPI, tossing weight, avoid carbo drinks**)

Question 5

5. A 45 year old patient complains of maldigestion, increasing abdominal pain and weakness. Abdominal discomfort occurs shortly after meals or alcohol ingestion. Laboratory results:

• Haemoccult: +
• anemia

What tests would you do, what are the treatment options?

Answer 5

• Positive hemoccult and anemia in 45 yr. old w/ abd. pain → maybe malignancy, but…
• Pain shortly after meals/alcohol → peptic ulcer is mostly likely
• May also be IBD (Crohn’s / UC)
• Tests :
  
  • Endoscopy + biopsy to check for presence of ulcer and culture it for H. pylori and alsoto differentiate between ulcer and cancer
  • Urea Breath Test - isotope-labelled urea solution is swallowed, if H. pylori is present, itsurease breaks down urea into isotope-labelled CO 2 which is detected in patient’s breath
  • If the above tests are negative for ulcer / H. pylori, use the tests mentioned in the nextquestion for IBD.
• Treatment :
  
  • If H. pylori positive → triple therapy : clarithromycin, amoxicillin and PPI

(**Abdominal discomfort occurs shortly after meals - typical for … (ulcer)Haemoccult: + (peptic ulcer have a tendency to bleedother: gastroscopy+biopsy (h.pylori, gastric cancer biopsy)Differential: - Drugs NSAID - ….**)

Question 6

6. What tests would you perform if you suspect your patient has an autoimmune inflammatory bowel disease?

Answer 6

• If patient has not already reported visible blood in stool → hemoccult
• Colonoscopy/endoscopy with biopsy - always done for suspected UC or Crohn’s
• If nothing is found via colonoscopy/endoscopy, can perform capsule endoscopy
• Stool culture + microscopy to rule out microbial/helminthic infection
• Systemic inflammatory markers such as CRP or ESR
• Antibodies can be tested such as ASCA (anti-S. cerevisiae, common in Crohn’s) and p-ANCA (common in UC)

(**Chron’s / Colitis ulcerosa (diagnosis: endoscopy [biopsy: histologically they are very different])Chron’s - transmural | Colitis ulcerosa - only mucosaChron’s - inf. anywhere |. (ileitis terminalis)| Colitis ulcerosa - Rectum/**)

Question 7

7. A 30 year-old man complains of recurrent abdominal pain usually accompanied with diarrhea. These symptoms occur after the ingestion of fresh dairy products or alcohol.

What may be the cause of these complaints? What tests would you do?

Answer 7

• This is lactose intolerance which can be worsened by alcohol, because it decreases lactase activity.
• Tests :
  
  • Lactose Hydrogen Breath Test - patient swallows a lactose solution and their breath ischecked every 20-30 mins for 2-3 hours against a baseline measurement for largeincreases in hydrogen gas
  • Blood Glucose Test - lactose malabsorbers will generally see less of an increase inblood glucose after ingesting lactose
  • Stool Acidity Test - for infants b/c they don’t cooperate with

(**Lactose intolerance(HBT)Alcohol - inhibits enzyme activity (worsen the symptoms)**)

Question 8

1. A 61 year-old man lost 8 kg during the last 4 months. He complains of pruritus and frequent dull epigastric pain. He has noted dark urine , but light stools lately. He has jaundice . The gallbladder is palpable, but non-tender.

Laboratory results:

serum bilirubin: 310 μmol/l, mostly direct

urine Ubg: negative

ASAT: 82 U/l

ALAT: 91 U/l

alkaline phosphatase: 540 U/l

prothrombin time: INR = 2.6

What is the cause of his jaundice? What further tests do you consider?

Answer 8

• Serum bilirubin is very high (>17 umol/l) and mostly direct, indicating direct hyperbilirubinemia (no issue with UDP-glucuronyl transferase)
• Lack of Ubg suggests total obstruction of bilirubin secretion into the GI tract
• ASAT/ALAT are high (>45 U/l) and ALP is very high (>150 U/l) indicating liver damage and significant obstruction , respectively
• Prothrombin time is long (>1.2 INR) indicating liver disease and/or biliary obstruction ( → improper vitamin K absorption → no γ-carboxylation of clotting factors)
• Weight loss in an elderly patient indicates malignancy (in younger pt, DM / anorexia / malabsorption / hyperthyroid)
• A palpable, non-tender gallbladder is the Courvoisier sign for pancreatic carcinoma (the enlarged head elevates the GB)
• Dark urine = direct bilirubin ; light stool = no stercobilin ; both indicate obstruction
• Endoscopic retrograde cholecysto-pancreatography
  
  • administer contrast to bile + pancreatic ducts to observe size of tumor
• Imaging (US, CT, MRI) to observe size of tumor + presence of metastases
• Administer IV vitamin K to resolve prothrombin time

Question 9

2. An icteric woman has the following laboratory parameters:

• serum indirect bilirubin: 54 μmol/l
• serum direct bilirubin: 5,1 μmol/l
• urine bilirubin: negative
• ASAT: 19 U/l
• ALAT: 22 U/l
• LDH: 720 U/l
• Ht: 0.33 l/l
• plasma haptoglobin and hemopexin concentrations are significantly decreased

What is the cause of her jaundice?

Answer 9

• indirect bilirubin is high; direct is normal indicating increased hemolysis with normal UDP-glucuronyl transferase function
• ASAT/ALAT are normal indicating no liver damage
• Urine bilirubin is absent (only conjugated bilirubin enters urine)
• LDH is high indicating hemolysis (specifically LDH1 from RBCs)
• Ht is low (<0.37 l/l) indicating anemia/hemolysis
• Haptoglobin/hemoplexin are proteins which bind broken down Hb in the blood, ↓ indicates intravascular hemolysis
• So the cause of jaundice is intravascular hemolysis , but the cause of hemolysis is unknown and must be determined.
• Can check for viral / autoimmune (RA/SLE) / allergic (penicillin) / etc. causes

Question 10

3. A 38 year-old man, who regularly drinks alcohol. He has never been ill before (acute!) , but he has grown icteric in the last couple of days. He has a temperature , and is a little anemic. His liver is palpable an inch below the ribs, it is slightly tender.

Laboratory results:

• urine color: dark brown
• serum total bilirubin: 150 μmol/l
• ASAT: 160 U/l
• ALAT: 60 U/l
• GGT: 490 U/l
• MCV: 103 fl

What is the cause of his jaundice?

Answer 10

• Dark brown urine indicates bilirubinuria (specifically direct, only direct goes to urine)
• Total bilirubin is high (>17 umol/l)
• ASAT/ALAT are elevated, with ASAT higher, indicating alcoholic liver damage
  
  • alcohol is a mitochondrial toxin → release of mitochondrial “mASAT”
• GGT is elevated (>60 U/l) indicating alcoholic liver damage
• MCV is high (>95 fl) indicating macrocytic anemia
  
  • due to vitamin B deficiency common in alcoholics via inflammatory malabsorption + malnutrition
• acute symptoms indicate this is not cirrhosis → acute alcoholic hepatitis is the cause of jaundice

Question 11

4. A 47 year-old man has been on hemodialysis for 5 years before he got his kidney transplantation . He has little body hair , a large, protruding belly , slim extremities and gynecomastia.

Laboratory results:

• ASAT: 85 U/l
• ALAT: 76 U/l
• prothrombin time: INR = 2.7; it does not change after vitamin K administration
• albumin: 28 g/l
• K+: 3.3 mmol/l
• Ht: 0.36

What is the most likely diagnosis?

Answer 11

• equally, but not extremely elevated ASAT/ALAT (>45 U/l) indicate chronic non-alcoholic liver damage
• elongated PTR (1.2 INR) unresponsive to vit. K indicates liver damage → coag. factor deficiency
• decreased albumin (< 35 g/l) indicates liver dysfunction
• dialysis is a risk factor for iatrogenic hepatitis
• low K + (<3.5 mM) probably via:
  
  • ascites (“protruding belly”) → ↓ circulating fluid volume → activation of RAAS in kidney → ↑ aldosterone → ↑ K + excretion
• low Ht (<0.4 l/l) via anemia , common in liver disease
• “effeminate” body constitution (↓ hair, breasts, slim limbs) indicates liver dysfunction
• This is most likely cirrhosis via a chronic iatrogenic hepatitis from dialysis.
  
  • Blood transfusions are common after dialysis, and can lead to hepatitis C infection (according to Hamar).

Question 12

5. A 38 year-old woman complains of recurrent, sharp pain in the right upper quadrant of her abdomen. She has been vomiting , has fever and jaundice .

Laboratory results:

• serum bilirubin: 50 μmol/l, mostly direct
• Ubg: negative
• ASAT: 180 U/l
• alkaline phosphatase: 640 U/l

What is the cause of her symptoms, and how can you prove the diagnosis?

Answer 12

• High, mostly direct bilirubin (>17 umol/l) indicates obstructive jaundice
• Negative Ubg also indicates obstructive jaundice (no bilirubin → GI tract)
• ASAT elevation (>45 U/l) indicates liver damage
• ALP elevation (>150 U/l) indicates obstruction
• Sharp RUQ pain indicate possible gallstones
• Vomiting and fever indicate possible cholecystitis
• Prove the possibility of cholelithiasis with abdominal ultrasound .

Question 13

6. A 25 year-old man has been icteric for a few days.

His laboratory values:

• serum indirect bilirubin: 47 μmol/l
• serum direct bilirubin: 4 μmol/l
• ASAT: 18 U/l ALAT: 23 U/l
• alkaline phosphatase: 66 U/l
• Ht: 0.48
• Hb: 162 g/l

What is the cause of his jaundice?

What further tests are necessary?

Answer 13

• Indirect bilirubin increase with normal direct indicates indirect hyperbilirubinemia (conjugation enzyme issue)
• Normal ASAT/ALAT/ALP indicate no liver damage/obstruction
• Normal Ht/Hb (>0.4 l/l and >135 g/l) indicates no hemolysis
• This is Gilbert syndrome , slightly decreased UDP-g transferase activity. Only slightly increased indirect bilirubin is seen, with no other abnormal findings.
• Test : No further tests are necessary, but Tunde says you can do this (if you hate your patient):
  
  • Have the patient fast (<1000 kcal/day) for 2 days and then measure indirect bilirubin. If it has doubled from your initial measurement, this confirms Gilbert’s syndrome.
  • (Acute stress can cause otherwise “silent” Gilbert’s to show symptoms. This test simulates that effect.)

Question 14

7. A 32 year-old man has been complaining of fatigue, malaise and a temperature for a week. His liver is palpable ¾ of an inch below the ribs, it is a bit tender.

His laboratory results:

• serum indirect bilirubin: 28 μmol/l
• serum direct bilirubin: 24 μmol/l
• Ubg: increased
• ASAT: 870 U/l
• ALAT: 1180 U/l
• alkaline phosphatase: 310 U/l

What is the most likely diagnosis, and how can you prove it? What further tests are necessary?

Answer 14

• Equal direct + indirect bilirubin elevation → hepatocellular jaundice
• Ubg increase → not obstructed , Ubg production in GI tract
• ASAT/ALAT/ALP elevation → liver damage
  
  • High ALAT/ASAT ratio particularly indicates viral hepatitis as the cause of damage
• Palpable, tender liver + fatigue/malaise/fever → acute hepatitis
• Check for Hep A/B/C antigens/antibodies
  
  • If A → check family
  • If B/C → check sexual partners + recheck patient after 6-8 months
    
    • If antigens still high after 6-8 months, start antiviral therapy to avoid chronic hepatitis + cirrhosis

Question 15

8. A 28 year-old woman. She is complaining of fatigue , malaise and nausea .

• serum total bilirubin: 45 μmol/l
• ALAT: 220 U/l
• alkaline phosphatase: 200 U/l
• γ-globulins: 33 g/l (↑)
• RF and ANA: positive

What is the most likely diagnosis, and what tests should be done?

Answer 15

• Increased total bilirubin (>17 umol/l) → hyperbilirubinemia
• Elevated ALAT/ALP (>45 U/l) → liver damage , possibly obstructive
  
  • Some complaints could be due to pregnancy (fatigue, malaise, nausea) and ALP is increased in pregnancy. A more specific test for liver damage would be GGT .
• RF/ANA → SLE
• γ-globulin increase indicates excess circulating antibodies
• This is most likely systemic lupus erythematosus causing an autoimmune hepatitis.
• Check other antibodies: anti-Smith antigen (RNA-binding protein) and anti-cardiolipin
• It is possible, but rare, for Hep B/C to induce the formation of RF/ANA, so must rule these out.

Question 16

9 . A 30 year-old woman, who is 164 cm tall, her body weight is 81 kg . She saw her doctor, because she had noted a yellow discoloration of her skin accompanied by itching . She mentions she has had unpleasant gastrointestinal symptoms after meals for a long time: feeling full , having nausea . Physical examination reveals: yellow skin and sclera , spleen is not palpable , liver enlarged by an inch. The right upper quadrant of her abdomen is clearly sensitive on palpation.

Laboratory findings:

• serum bilirubin: 150 μmol/l
• urine bilirubin: positive
• Ubg: decreased
• ASAT: 53 U/l
• alkaline phosphatase: 710 U/l
• GGT: 390 U/l

What is the most likely diagnosis?

Answer 16

• High bilirubin + urine bilirubin → hyperbilirubinemia , of conjugated type b/c only conjugated gets to urine
• Ubg decrease → obstruction , no bilirubin to GI tract
• ASAT is slightly increased → mild liver damage
• ALP is very high (>150 U/l) → obstruction
• GGT is high (>60 U/l) → obstruction
• Obstructive jaundice has two common possible causes: malignancy or cholelithiasis
• In a young (30 yr old) and overweight (81 kg @ 164 cm) patient, gallstones are the most likely cause
• Perform abdominal ultrasound.

Question 17

10. A newborn baby is admitted to the hospital with a complaint of increasing jaundice. The serum bilirubin is 160 μmol/l.

What can be the cause of the jaundice if this bilirubin is mainly:

1. direct, or
2. indirect reacting?

Answer 17

1. Causes of direct hyperbilirubinemia:
   
   • Infection - hepatitis or any other infection can ↓ liver function
   • Biliary atresia - improper development of bile ducts
   • Dubin-Johnson Syndrome - AR mutation of canalicular MRP2 → ↓ hepatic excretion of bilirubin glucuronide (liver appears black)
   • Rotor Syndrome - AR mutation of OATP1B (organic anion transporting polypeptide) proteins for hepatic uptake of of bilirubin
2. Causes of indirect hyperbilirubinemia:
   
   • Physiological jaundice - before birth glucuronyltransferase is downregulated in the fetus to keep bilirubin unconjugated and thus able to pass through the placenta and not accumulate in the fetus; it takes some time to fully function after birth b
   • Erythroblastosis fetalis - via Rh incompatibility → hemolysis
   • Gilbert’s Disease - low UDP-g transferase function, often asymptomatic unless stressed
   • Crigler-Najjar - 2 types: total or partial lack of UDP-glucuronosyl transferase
     
     • severe form can lead to kernicterus (bilirubin in brain) → brain damage
       
       • only treatment is liver transplant
     • phenobarbital can induce the enzyme in the less severe form
   • Phototherapy can be used to solubilize excess dermal bilirubin in neonatal jaundice.

Question 18

1. A 25-year-old woman has been admitted because of a severe dyspnea of sudden onset. She mentions that she wakes up at night because of coughing lately. She also noticed a wheezing sound occasionally, during respiration. She is allergic, she has been smoking for 5 years, 5 cigarettes/day.

Physical examination: diaphragm is found low by percussion, exhalation is prolonged, with a bit of wheezing at the end.

Pulmonary function tests:

• *FVC:** 3.02 l (80%)
• *FEV1**: 1.52 l (45%).

Reversibility test with Salbutamol:

• *FVC**: 3.52 (95%)
• *FEV1**: 1.75 l (62 %)

What is the most likely diagnosis?

Answer 18

• Pulmonary function test is low
• Reversibility test: there is improvements of FEV1 after salbutamol (bronchial dilator):

the obstruction is temporarily and reversible. Suggest asthma.

• Key: allergy frequently precedes development of asthma.
• FVC > 80 %
• FEV1: > 80 %
• Symptoms of asthma: chronic inflammatory disorder of the airways

o Recurring episodes of wheezing, breathlessness, chest tightness, and coughing, particularity at night or in the early morning.

Paroxysmal nocturnal dyspnea is due to respiratory depression during sleep worsening the already present pulmonary issues

the minimum difference in % between FVC taken before and after Reversibility test to make a confident diagnosis of asthma. The answer is 15%.

TYPES

atopic,
non-atopic,
drug-induced
and occupational asthma.

o Risk factors: house dust mites, animals with fur, pollens, respiratory (viral) infections, exercise, strong emotional expressions, chemical irritants, drugs (such as aspirin and beta blockers) etc.

Question 19

A 67-year-old man complains of coughing. He is currently producing a lot of yellowish- greenish sputum, that is more than the amount he usually has. It is hard for him even to get to the toilet, because of his severe dyspnea. He has been treated for hypertension and hyperlipidemia for years. He weighs 100 kg. He has been smoking since the age of 14, around 30 cigarettes/day.

Physical examination: his lips are markedly cyanotic, exhalation is prolonged with occasional wheezing at the end. Bronchial ronchi can be heard.

ABG:

pH: 7.35
pCO2: 43 mmHg
pO2: 54 mmHg

Pulmonary function tests:
FVC 2.12 l (52 %)
FEV1: 0.97 l ( 32%)
TLC: 5.24 l (105%)

RV: 3.27 (176%) Raw: 0.87 kPa·s/l.

Reversibility test with Salbutamol:
FVC: 2.19 l (54%)
FEV1: 1.01 l (33 %)

What sort of ventilatory defect is present? What is the most likely diagnosis?

Answer 19

Calculated TI = 62%

Semi-old man, buckets of sputum, 80 pack years.

High risk of COPD, symptoms of Chronic Bronchitis

Cyanosis, prolonged exhalation and wheezing fit with obstructive disease

Should check chest diameter, patients with Chronic Bronchitis can have a “barrel chest” (barrel chest + cyanosis → “Blue Bloater” chronic bronchitis phenotype)

• In this case he has increased amount of sputum: looks like an acute upper respiratory inflammation
• Suggest obstructive lung disease: blue bloater?
• pO2: low
• pCO2: not so high, should be high in chronic bronchitis.
• There is an acute worsening of the condition: probably hyperventilation, that brings pCO2 back to near normal.
• Pulmonary function test: very bad

o FVC and FEV1: is very low
o TLC and RV: is increased
o RAW: resistance of airways: probably low.

• Reversibility test: no difference, which means it is not asthma.
• Ventillatory defect: obstructive disease

- Chronic bronchitis, with acute worsening of the condition.

- Chronic bronchitis

Raw = Rairway isn’t really mentioned elsewhere, but Hamar says we only need to know that it is an abbreviation for airway resistance, and it’s increased because of the obstruction.

Salbutamol-test shows 2% and 1% increase in FVC and FEV1, disproving asthma

Diagnosis: Severe COPD

o Chronic cough associated with sputum production more than 90 days on 2 successive years.

o Cause:
Smoking, air pollution, occupational exposure, etc.

Question 20

3. A 55-year-old woman complains of hardening of her skin, having fissures on her hands. She has been avoiding climbing stairs for years due to breathlessness. Her dyspnea got much worse in the last few years. Auscultation of the lungs does not reveal any abnormality. Chest radiography shows increased opacification on both sides, mostly at the bases, above the diaphragm. The heart appears enlarged to the right, the pulmonary trunks are thicker on both sides.

Pulmonary function tests:
FVC: 3.01 l (64 %)
FEV1:2.75 l (68%)
TLCO:54 %

KLCO: 45%

ABG at rest (Arterial Blood Gas) :

pH: 7.38
pCO2: 38 mmHg
pO2: 81 mmHg

ABG after 6 min of exercise:

pH: 7.42
pCO2: 34 mmHg
pO2: 75 mmHg

ECG: signs of right ventricular strain, P pulmonale

What sort of ventilatory defect is present? What additional tests should be performed? What is the possible diagnosis?

Answer 20

Middle-aged woman, hardening skin and fissures could be CREST/Scleroderma[1]

Progressively worse exertional dyspnoea could be anything, but fits with Scleroderma

CXR shows bilateral opacification of the bases of the lungs which is indicative of interstitial lung disease

The RVH is due to pulmonary hypertension caused by the chronic pulmonary fibrosis

Pulmonary Function tests show decreased FVC, FEV1 and increased TI

FEV1 ≤ 80%, FVC ≤ 80% and TI ≥ 70% is indicative of restrictive disease

This fits with scleroderma

TLCO (Transfer factor of the Lung for CO) is aka DLCO
(Diffusion lung capacity for CO). (normal is 81-140%)

This is the result of a Gas Transfer Test, using CO because it has a similar diffusion capacity to O2.

TLCO is decreased in any condition which affects the effective alveolar surface area, this patient’s decreased TLCO fits with Scleroderma

KLCO (TLCO corrected for alveolar volume) should be lower than TLCO.

A KLCO that is higher than TLCO indicates that the restriction is extrapulmonary.

In this this patient the KLCO is lower than TLCO disproves extrapulmonary restriction (obesity, kyphoscoliosis, ascites)

ABG:

paO2 is decreased in rest. Exercise shows that compensation to strain is insufficient.

paCO2 decreasing below normal values (35-45 mmHg) shows that she is hyperventilating. CO2 has a much higher diffusion capacity than O2, because of the pressure-gradient, and so is easily “excreted” even though she has a reduced alveolar volume. However O2 hit its diffusion capacity even before exercise (she was hypoxemic at rest), and paO2 continues to decrease.

ECG: RV strain due to hypoxia, p pulmonale due to pulmonary HTN, which again, is caused by the pulmonary fibrosis

Dx:Pulmonary tests, ABG and ECG point to Interstitial Lung Disease, which could be explained by systemic scleroderma (Autoimmune hyperproduction of Collagen[2] ).

Check autoantibodies to confirm (local form has anticentromeric Ab, diffuse has anti-topoisomerase Ab) also anti-RNAP 3

Systemic Scleroderma reaching the lungs indicates a 70% 5-year survival

There is no cure, however it was mentioned that you can treat/ alleviate symptoms with anti-fibrotic drugs and immunosuppressants.

CREST refers to limited scleroderma, just from the fact that there is hardening of skin cant exclude it. But because of the lung involvement this is systemic (diffuse) scleroderma.

autoimmune disease leading to fibroblast overactivation -> overproduction of collagen

Question 21

4. A 72 year old man presents at the ambulance due to severe dyspnea. He has a history of longstanding hypertension, two AMIs and coronary artery disease. At his admission he complains of progressing postural dyspnea

RR: 160/100, heart rate: 108/min, rate of respiration: 22/min.
Blood gas: pH: 7,36, pCO2: 40 Hgmm, pO2: 72 Hgmm, O2 saturation (without oxygen supplementation): 88%.
ECG: signs of LVH, ST elevation and significant Q waves in the anterior and lateral leads.
What other diagnostic tests would you indicate? What type of disease(es) could this patient have?

Answer 21

….

Question 22

5. A 57 year old man four days after his knee replacement surgery complains of sudden, severe dyspnea and pain on the left side of his chest.

RR: 110/70, heart rate: 120/min, respiration rate: 28/min. Physical examination finds normal heart and lung status, the right lower limb is edematous, tender, erythematic and is warm compared to the left lower limb.
Blood gas: pH: 7,36, pCO2: 40 Hgmm, pO2: 72 Hgmm, O2 saturation (without oxygen supplementation): 78%.

What other diagnostic tests would you indicate? What is the possible diagnosis?

Answer 22

….

Question 23

1. Some weeks after having a sore throat and high fever, the patient has developed edema. His blood pressure is increased.

Urinalysis:

• *volume:** 450 ml/day !!!
• *protein**: +++ (3 g/day)
• *sediment**: 50–100 erythrocytes/HPF, leukocytes rarely
• *creatinine clearance**: 30 ml/min

What is the presumable diagnosis?

Answer 23

Low urine volume (normal: 1-1.5L/day)

Considered oliguria because it’s between 200 and 500 mL/day. Below 200 mL is considered anuria.

+++ = Large proteinuria

(normal is 50-150 mg/day. Pathological if > 300mg/day. Considered “massive proteinuria” if > 3 g/day)

Causes edema from the reduced capillary colloid osmotic pressure

Sediment shows hematuria / significant red blood cells in the urine

(considered microscopic hematuria is >3 RBCs per high power field)

Very Low GFR (normal creatinine clearance is 120-125 mL/min)

Kidneys are failing to properly filter the blood, probably due to glomerular inflammation

Low GFR ⇨ water retention ⇨ hypertension, both of which also contribute to edema

Diagnosis: Nephritic Syndrome based on hematuria
(if it was only protein and no blood, then it would be nephrotic syndrome)

Probably due to post-streptococcal glomerulonephritis

(upper respiratory infection, then weeks later ⇨ glomerulonephritis with immune complex deposition in glomeruli, between the basement membrane and podocytes. Immune complexes activate the complement system, causing inflammation and damage to the filtration barrier, allowing proteins to leak into the urine)

Question 24

2. Laboratory findings of a patient with massive edemas:

serum total protein: 40 g/l

serum cholesterol: 10 mmol/l

ESR: 28 mm/h

blood pressure: 125/80 mmHg

Urinalysis:

quantity: 1800 ml/day
protein: ++++ (12 g/day)
sediment: 1–2 leukocytes/HPF, erythrocytes rarely, a lot of hyaline casts

What is the presumable diagnosis?

Answer 24

Very Low Serum Protein (normal is 60-80 g/L)

Causes edema due to reduced capillary colloid osmotic pressure

High Serum Cholesterol (normal 3.6-5.2 mmol/L)

Exact mechanism of why this occurs is unclear, but whenever the kidney loses a lot of proteins, the liver synthesizes more proteins - including VLDL. Also LDL is probably big enough to not be filtered by the kidney, and so remains in the bloodstream.

Increased ESR (normal is < 20 mm/hour)

Low serum protein means there are fewer negative charges in the blood (especially due to albumin loss), and those charges normally repel the negative charges on the RBCs. This repelling effect (or “zeta potential”) normally makes the rate at which RBCs settle (erythrocyte sedimentation rate) fairly slow. With reduced zeta potential, red blood cells are able to settle at a faster rate (Zeta Potential↓ = ESR ↑)

Normal Blood Pressure (helps rule out other causes of edema besides proteinuria)

Normal Urine Volume (normal is 1-1.5 L/day) Technically this is higher than the 1.5 L/day range on their lab values sheet, but only 300 mL more is not significant.

Massive Proteinuria (normal is < 300 mg/day, and it’s already considered massive proteinuria at > 3 g/day… 12 is very high)

No hematuria: Only a few RBCs seen

Diagnosis: Nephrotic syndrome based on massive proteinuria with edema, hyperlipidemia, and no blood in the urine. Doesn’t tell you anything about what could have caused the nephrotic syndrome.

Extra: Possible causes of nephrotic syndrome:

Primary Glomerulonephrosis:

effects limited to kidney; many different causes + histological manifestations; mostly due to immune complex deposition (often autoimmune), toxins or drugs.

Secondary Glomerulonephrosis: systemic effects with kidney involvement

Diabetic Nephropathy - renal damage from hyperglycemia, AGE

Auto-immunity - seen in SLE (“lupus nephritis”), Sjogren’s, AI vasculitis; immune complex deposition → renal damage

Infections - syphilis, Hep B, HIV

Multiple Myeloma - accumulation/precipitation of light chains → cast formation → obstruction + toxicity

Other Cancers - invasion of glomeruli by cancer cells

Amyloidosis / Sarcoidosis - accum. of amyloid / inflamm. granulomas, respectively (renal involvement rare, but possible, in sarcoidosis)

Genetic - congenital nephrotic syndrome, mutated nephrin filtration barrier protein

Drugs - penicillin, captopril

Question 25

3. A febrile patient complains of lumbar pain.

Urinalysis:

protein: ++
pus: +++
sediment: a lot of leukocytes, some erythrocytes, epithelial cells, a lot of bacteria, leukocyte casts

C_K: 100 ml/min
ESR: 38 mm/h

What is the presumable diagnosis?

Answer 25

Moderate protein in urine: (normal < 300 mg/day / day). Some glomerular damage

Pyuria: pus in urine, sign of urinary tract infection (E.coli , enterofaecalis)

Leukocytes in urine indicates infection, while RBCs and epithelial cells indicate damage

Leukocyte casts indicate pyelonephritis, as they are made in the tubular system.

Slightly Low C_K: some impaired kidney function

Increased ESR: (normal is < 20 mm/hour)

ESR normally is increased with inflammation due to acute phase protein synthesis, specifically that the increased serum fibrinogen causes RBCs to clump together and settle at a faster rate.

Diagnosis: Pyelonephritis.

Pyelonephritis usually is the result of **ascending urinary tract infection.

Lumbar pain**
occurs due to inflammation distending the renal capsule, and fever occurs due to organ infection stimulating systemic cytokine responses.

Examples include
albumin,[5]
transferrin,[5]
transthyretin,[5]
retinol binding protein,
antithrombin,
transcortin.

The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing “positive” acute phase proteins more efficiently.

Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptors, but the latter does not appear to change with inflammation.

Question 26

4. Laboratory findings of a patient include the following:

Urinalysis:

sediment: 3–5 erythrocytes/HPF, rarely leukocytes;

the erythrocytes are isomorphic;

minimal proteinuria; -the urinary protein electrophoresis does not show selectivity in the proteinuria

C_k: 120 ml/min

What can be the probable diagnosis: glomerular hematuria or urinary tract bleeding?

Answer 26

Diagnosis: Mild Urinary Tract Bleeding, probably from kidney stone (nephrolithiasis)

Slight Microscopic Hematuria: normal is < 3 erythrocytes / HPF

Normal Morphology (Isomorphic) RBCs: indicates the bleeding occurs more distally in the urinary tract

If there is glomerular damage where red blood cells enter the tubules for filtration, then the cells are present during the concentrating process, which dehydrates them ⇨ small, dysmorphic erythrocytes. That did not occur here, so the glomeruli and tubules are probably fine.

Minimal proteinuria: the equipment is not sensitive enough to show proteinuria < 300 mg / day : also suggest that it is not a glomerular bleeding, always goes together with a significant proteinuria

“No selectivity in the proteinuria”: since bleeding is likely distal in the urinary tract, no filtration barrier is involved. Blood leaks into the urine, and so all proteins can get in.

Normal Creatinine Clearance: GFR is not impaired

Question 27

5. After receiving a massive dose of aminoglycoside antibiotic, a patient with no prior symptoms of kidney disease develops a body weight gain of 3 kg over a period of 3 days. He does not void urine spontaneously. The total volume of urine collected by catheterization is 200 ml/day.

Other laboratory results:

serum creatinine: 440 μmol/l NB!!!

serum urea: 28.5 mmol/l +

plasma K : 6.2 mmol/l

What is the most likely diagnosis?

Answer 27

Tubular damage: Aminoglycosides are known to be toxic to the renal tubules

Weight gain due to water retention from extremely low urine output

Anuria < 200 mL urine / day

3 serum metabolite levels are all elevated, indicating retention due to renal failure:

Elevated serum creatinine: (normal 40-130 µmol/L)

Elevated serum urea: (normal 2 - 10 mmol/l)

blood urea nitrogen (BUN) is ‘carbamid’ on the pathophys ref. ranges document)

Hyperkalemia: (normal Se [K+] 3.5-5 mmol/L)

Diagnosis: Acute Renal Failure (ARF) due to aminoglycoside toxicity

Question 28

6. The serum glucose level is 15 mmol/l in a diabetic ketoacidosis.

GFR is markedly decreased (20 ml/min).

Tubular function tests are negative.

No glucose can be detected in the urine (by repeated tests).

How is this possible?

Answer 28

• If the GFR is decreased enough, the glucose load is also decreased.

Normally, glucose is reabsorbed in the tubules up until it reaches the BGL concentration of 10 mmol/L, at which point the SGLT transporters are saturated

In this case, the GFR is so low that glucose has time to be reabsorbed in the tubules by SGLT2 transporters, which are not damaged

• Less glucose per time is filtered into the renal tubules. This gives the patient _more time to reabsorb the glucos_e. Thus, glucosuria will not develop.
• If the GFR is very low, the patient will have a higher tubular threshold and the glucose will not be detected in the urine.
• Tubular function test: negative

-Concentration + dilution test: follow up!

Concentration test:

dinner without fluid and no drinking of fluid throughout the

night: urine in the morning is analyzed for its density. If the urine in morning is

not concentrated, it means that something wrong. It should be increased.

• *Dilution** test: drink 1-2 L tea or a large amount of fluid; then the urine sample should have low-density values, and low osmotic cc.→ If the urine is not diluted, so it does not go below 1,010 kg/l (density→ there is a problem with dilution of the urine
• Patient with chronic renal disease loose first the concentration capability and later they loose the dilution capability (end stage: cannot concentrate nor dilute – the urine osmolarity is the same as the urine – called isostenuria.

Question 29

7. Laboratory findings of a patient:

Urinalysis:
color: straw-yellow
transparency: turbid (nubecula)
quantity: 400 ml (present), 1600 ml/day
specific gravity: 1022
protein: 50mg/day
pus: +++
blood: +
glucose: neg
acetone: neg
ubg: norm
bilirubin: neg

Urinary sediment:

20–30 epithelial cells
30–40 WBC
3–4 RBC, per high power field

Further data:

body temperature: 38°C
WBC: 12 G/l
RBC: 4.5 T/l
ESR:2 mm/h

creatinine clearance: 120 ml/min,

cultivation of E. coli: positive

What is the most likely diagnosis?

Answer 29

Many normal findings are listed:

normal urine volume (being just above the “normal” 1.5L/day is not significant), normal specific gravity (1010-1035), no proteinuria (< 300 mg/day), no glucosuria (no diabetes), normal UBG and bilirubin (liver is OK), body temperature on the upper end of normal but it’s not a true fever, normal RBC count (4.4-5.5 T/l), ESR is < 20 mm/h, normal creatinine clearance (120-125 ml/min)

Diagnosis: Urinary Tract Infection from E. coli that has not ascended to become pyelonephritis

Color: seems to indicate significant pus

Pus +++: clear sign of infection

Microscopic hematuria: very small amount of blood. Never find out if RBCs are isomorphic for sure but they probably are since there is no renal glomerular/tubular involvement.

Epithelial cells in urine: also due to damage

Elevated WBC count: (normal 4-10 G/l) - usually increases with infection

Neutrophils in particular increase with bacterial infections

Positive E. coli Culture: makes the diagnosis of UTI easy.

No signs of systemic/organ infection → ESR is not elevated, no fever, etc.

Urinary tract infections do not normally cause fever unless the infection reaches the kidney.

Question 30

1. What is the direction of change in the parameters below during respiratory acidosis? During

Answer 30

Actual HCO3- - directly measured bicarbonate of the blood sample

Generation:

aHCO3- is dependent on both metabolism and respiration. In respiratory acidosis (not breathing sufficiently) pCO2 increases, and due to Le Chatelier’s principle more HCO3- is formed.

CO2 + H2O ←→ H2CO3 ←→ HCO3- + H+ (shifts rightward)

Compensation:

Standard HCO3-

Generation:

stHCO3- is only dependent on metabolism, because the value is measured after equilibrating the sample to 40 mmHg pCO2. There is initially no metabolic change (compensation), and thus no change in the value.

Compensation:
However, after the increase in HCO3- reabsorption we can see an increase in stHCO3-.
—————————————————————————————————————————-

Base excess (BE)

Generation:

this value shows base deficit reflecting the metabolic side, and initially there is no change in the metabolic side.

Compensation:

as explained above there will be an increase of HCO3- (base) due to kidney compensation, thus BE will show a positive value (pos. = base excess/lack of acids).

Note that compensation by the kidney takes maybe 6-8 hours before working, and up to 3-5 days before maximal effect. This is because synthesis of channel proteins in the kidney is needed for the compensation.

Question 31

3. Traumatic shock (bleeding, crush). The acid-base parameters

Answer 31

During first hours

pH indicates acidemia (normal is 7.35-7.45)

HCO3- indicates of metabolic origin (normal is 24 mmol/L)

AG cannot be determined. Cannot calculate corrected HCO3- without AG.

pCO2 is low (normal 35-45 mmHg), but expected pCO2 = 18-22 mmHg according to Winter’s formula (below).

• pCO2 measured is within this range, thus compensation is normal.
• Winter’s formula is used to calculate the expected pCO2 in respiratory compensation of an acid-base disorder, and its results are sometimes approximated as pCO2 ≈ last 2 digits of pH: pCO2 = (1.5 x HCO3-) + 8 +/- 2

BB is low (normal 45-52 mmol/L) because bases in blood are used up as buffers.

BE is strongly negative (normal 0 +/- 2.5 mmol/L) - lack of base, excess of acids

Conclusion: Primary metabolic acidosis with normal respiratory compensation.

One day later

pH indicates acidemia

Both pCO2 & HCO3- indicates acidosis

Expected pCO2 = 25.5-29.5,

• pCO2 measured is higher than the expected value, thus there is a coexisting respiratory acidosis. >50 mmHg -> hyperkapnia.

No change in BB or st.HCO3- can indicate lack of kidney compensation? (just something I believe)[1] [2] [3] [4] [5]

Conclusion:

the original metabolic acidosis has worsened due to inadequate lung compensation because of ARDS (referred to as “shock lung” in the question).

• *Metabolic acidosis + respiratory acidosis**​

Question 32

2. Diabetic ketoacidosis. How and why do the indicated parameters deviate from normal?

pH,

pCO2,

BE,

aHCO3–,

st HCO3–,

AG, se K+

Answer 32

- Diabetic ketoacidosis:

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances.

• DKA results from a shortage of insulin; in response the body switches to burning fatty acids and producing acidic ketone bodies that cause most of the symptoms and complications.

pH,

will decrease because of ketones (acetoacetic acid & beta-hydroxybutyric acid), but as compensatory mechanisms start to work it will become less acidic. However, if the DKA is not treated, more ketone bodies are produced and thus acidosis will worsen.

pCO2,

changes in pCO2 are related to compensation, so initially there is no change. As ventilation is increased to decrease H+, pCO2 will decrease.

• Patients with DKA typically present with Kussmaul breathing pattern (rapid & deep).

BE
will be strongly negative (acid excess / lack of base), but when the kidney starts compensating there will be an increase of HCO3- and thus a bit less negative value

• *aHCO3**
• *-**as there is an increase of H+, HCO3- will be depleted as a buffer.

As pCO2 decreases via lung compensation, aHCO3- will decrease further (again via Le Chatelier, the ↓ pCO2 shifts the carbonic anhydrase equation away from bicarb production).

• As HCO3- is reabsorbed, because of kidney compensation there is a slight increase in its serum concentration.

st HCO3
–will also be depleted as a buffer, is not affected by the lung compensation, and is also increased due to kidney reabsorption.
———————————————————————————————————————
AG
high due to increased amount of anions (ketones) not accounted for in the formula.

se K+, increased:

Insulin is a stimulator of the Na+/K+-ATPase, thus lack of insulin will lead to decreased cellular uptake.

Note that from this mechanism there is not an increase in the total body potassium, just a change in its distribution.

Most somatic cells have a H+/K+-exchanger, in acidosis there is a tendency for cells to use this to take up H+ and excrete K+, also resulting in movement of potassium extra cellularly.

Question 33

4. A 35-year-old woman reports to the ED with shortness of breath. She has cyanosis of the lips.

She has had a productive cough for 2 weeks. Her temperature is 39 oC, blood pressure 110/76 mmHg, heart rate 108 bpm, respirations 32/min, rapid and shallow. Breath sounds are diminished in both bases, with coarse bronchi in the upper lobes.

Her ABG results are:
pH = 7.44
pCO2 = 28 mmHg

aHCO3− = 18 mmol/l

stHCO3− = 20 mmol/l

AG = 12 mmol/l

pO2 = 54 mmHg

How do you interpret her ABG result? What other test would you order to verify your diagnosis?

Answer 33

Dyspnea and cyanosis is indicative for respiratory failure, which could be hypoxia (pO2 <60 mmHg) or hypercapnia (pCO2 >50 mmHg).

As you can see on the lab values, this respiratory failure is caused by hypoxia, thus a hypoxic respiratory failure (type I).

Productive cough and fever indicates an infection, this in combination with low BP, high HR and high resp. rate points towards a septic shock.

ABG results:

pH
is in the upper range of normal, but not alkalemia, can however argue that it is the start of an alkalosis (alkalizing process in the body).
—————————————————————————————————————————–

pCO2
is lower than the normal range (35-45 mmHg), which will increase the pH.

• Can be explained by the high resp. Rate.

—————————————————————————————————————————pO2

is at hypoxic levels (n: 80-105 mmHg), which could be explained by a pneumonia/sepsis → inflammation →pulmonary edema.

Due to the lower diffusion potential of O2 compared to CO2 (20 times lower),
pO2 decreases more than pCO2 increases.

The patient experience an increased ventilatory drive, but in the attempt to normalize the pO2 → hyperventilation → decrease pCO2 → respiratory alkalosis.
—————————————————————————————————————————aHCO3-
is lower than normal (21-26 mM), which would decrease the pH, thus indicative of metabolic acidosis.
—————————————————————————————————————————–stHCO3-
is only slightly lower than normal.
—————————————————————————————————————————–AG
is normal (10-14 mM), which means there are no additional anions not accounted for → “non-AG” or “hyperchloremic acidosis”
—————————————————————————————————————————–

Expected pCO2 = 33-37,

measured value is much lower indicating an additional respiratory alkalosis.

Corrected HCO3- = 18 mM, so there is an additional metabolic acidosis.

(Corrected HCO3- is calculated with the following formula, and if < 22 mM indicates an additional metabolic acidosis:

Conclusion:

Hypoxic respiratory failure due to pulmonary edema caused by pneumonia or sepsis (pt. fulfills 3 of the SIRS criteria, with leukocytosis being unknown).

What other test would you order to verify your diagnosis?

Chest x-ray - confirm pneumonia

Culture - to identify causative agent →targeted therapy

Blood work - to check ESR, acute phase proteins (e.g.: CRP), WBC count

Question 34

5. A 23 year-old woman with exacerbated rheumatoid arthritis enters to the ED. She has frequently vomited lately. Her medication: Aspirin 3–5 pills/day.

Her ABG result:

pH = 7.70

pCO2 = 25 mmHg

aHCO3− = 30 mmol/l
AG = 22 mmol/l
(Calculated pCO2 = 42–44 mmHg.)

What kind of acid-base disorders does she have?

Answer 34

RA can be treated with aspirin as in this case, as a side effect it can induce nausea and vomiting.

Vomiting causes loss of H+, thus increasing pH.

3-5 pills/day indicate aspirin overdose (NOT SURE WHAT THE LIMIT IS)

ABG results:

pH indicates alkalemia

pCO2

is lower than normal, thus increasing pH.

• Aspirin overdose triggers rapid and deep breathing.

aHCO3-
is higher than normal, thus increasing pH. Due to loss of H+ by vomiting.

AG is 22 mM,

if AG > 20 mM then there is a primary metabolic acidosis regardless of pH or HCO3-. As aspirin is an acid not accounted for in the AG formula it is probably the causes of the gap.

Expected pCO2 is 51-55, the measured value is lower than this, thus pt. has an additional respiratory alkalosis.

• *Corrected HCO3
• is40 mM, because> 26mMthere is anadditional metabolic alkalosis.**

Conclusion:

This is a complex picture caused by aspirin overdose, AKA “salicylate poisoning”:

Triggers nausea and vomiting, thus loss of H+ (additional metabolic alkalosis)

Triggers rapid and deep breathing and thus a respiratory alkalosis.

Aspirin in it self is an acid, thus causing the high anion gap and primary metabolic acidosis.

So primary metabolic acidosis with co-existing respiratory and metabolic alkalosis.

Question 35

6. A 60-year-old male presents to the ED from a nursing home. He has been breathing rapidly and is less responsive than usual. There is nothing else remarkable in the anamnestic data. His serum electrolyte panel and ABG:

Na+ = 123 mmol/l

K+ = 3.9 mmol/l

Cl− = 99 mmol/l

pH = **7.31**
pCO2 = **10** mmHg

aHCO3− = 5 mmol/l

(Calculated pCO2 = 13.5–17.5 mmHg)

What kind of acid-base disorders does he have?

Answer 35

Clinical findings:

Rapid breathing and less responsiveness cannot be explained from only this clinical anamnesis.

Laboratory findings:

[Na+] is lower than normal (135-145mM), [K+] & [Cl-] are within normal ranges.

• *pH** indicates acidemia

aHCO3-
is severely decreased, indicating a metabolic acidosis.
—————————————————————————————————————————

• *pCO2**
• *low,** probably due to rapid breathing as compensation.

AG
(123 - (99 + 5)) = 19 mM, is higher than normal,

• indicates primary anion gap metabolic acidosis.

• *Expected pCO2** =
• *13.5-17.5** the measured value is less than this,
• thus there is a coexisting respiratory alkalosis.

Corrected HCO3- = 12 mM,

• since < 22mM there is an coexisting metabolic acidosis.

Conclusion:

This patient has hyponatremia + primary anion gap metabolic acidosis with hyperventilation making a coexisting respiratory alkalosis, and also coexisting metabolic acidosis.

Hyponatremia can explain the unresponsiveness as it causes confusion and lethargy;

rapid breathing due to respiratory compensation of acidosis.

Addisons ?

probably was an ecstasy overdose ( ONE LILAC AIRWAYS GUM PUH-LEASEEE)

Question 36

7. A 42 year-old type 1 DM female has flu for four days with incessant vomiting. She presents to the ED two days after stopping insulin due to no food intake.

Her serum electrolyte panel and ABG:

Na+ = **130** mmol/l
K+ = **5.5** mmol/l
Cl− = 80 mmol/l

glucose = **15** mmol/l
pH = **7.21**
pCO2 = **25** mmHg
aHCO3− = **10** mmol/l

(Calculated pCO2 = 21–25 mmHg)

What kind of acid-base disorders does she have?

Answer 36

Clinical findings:

Type 1DM with no food intake or insulin for two days highly suggests diabetic ketoacidosis.

The extra stress associated with a flu can also trigger a DKA. Without insulin cells are not able to take up glucose and thus they are in starvation. The liver starts producing ketone bodies which are acidic.

Laboratory findings:

[Na+] is low (n;135-145mM),
[K+] is high (n:3,5-5,0 mM),
[Cl-] is low (n:95-105 mM)

As both ketones and glucose are osmotically active, an increase in ECF can explain the low sodium and chloride (relative decrease).

((( Polyuria would also occur due to osmotic diuresis, then the kidney would not be able to reabsorb sufficient Na+, and as Cl- is reabsorbed by electrical gradient caused by sodium it makes sense that it is also not reabsorbed sufficiently???)))

Lack of insulin decreases the activity of Na+/K+-ATPase which can explain the increase in potassium (also decrease in sodium?).

In addition, due to high H+ concentrations in acidosis, cells can use the H+/K+-exchanger to take up H+ and thus increasing EC potassium.

Fasting glucose (not eaten for two days) is too high (n:3,0-6,0), indicating that there is no uptake of glucose in the periphery and gluconeogenesis in the liver.

pH indicates acidemia.

• *aHCO3**
• indicates a metabolic source for the acidosis.

pCO2
is low, indicating respiratory compensation

AG
(130 - (80+10)) = 40 mM, AG > 20 mM indicates primary metabolic acidosis no matter HCO3- & pCO2 values.

Expected pCO2 = 21-25 mmHg, measured pCO2 is within this range - indicating normal respiratory compensation

Corrected HCO3- = 38 mM

• Because this is > 26 mmol/L, it indicates coexisting metabolic alkalosis
  (here being the excessive vomiting, expelling stomach acid)

Conclusion:

Diabetic ketoacidosis (primary anion gap metabolic acidosis) with normal respiratory compensation + coexisting metabolic alkalosis from vomiting.

Hyponatremia, hyperkalemia and hypochloremia.

Question 37

8. A 30-year-old female bone marrow transplanted patient with neutropenic fever has been receiving multiple antibiotics including amphotericin B. She developed rigors and dyspnea.

Her serum electrolyte panel and ABG:

Na + = 125 mmol / l
K + = 2.5 mmol / l
Cl− = 100 mmol/l
pH = 7.07
pCO2 = 28 mmHg
aHCO − = 8 mmol/l.
(Calculated pCO2 = 18–22 mmHg.)

What kind of acid-base disorders does she have?

Answer 37

Clinical findings:

Patients receiving BM transplants are immunocompromised, thus infections are common and normally “innocent” infections can become life threatening.
Antibiotics is given for bacterial- and amphotericin B for fungal infections.
Some antibiotics have side effects, for example being nephrotoxic (e.g.: amphotericin, aminoglycosides) possible causing ARF from tubular toxicity.

Rigors are typical for electrolyte disturbances.

Dyspnea has many causes, but here seems to be due to a respiratory infection being treated with antibiotics and amphotericin B..

Laboratory findings:

• *[Na+]** is low (n:135-145mM),
• *[K+]** is low (n:3,5-5,0 mM),
• *[Cl-]** is normal (n:95-105 mM)

pH is severely low, indicating acidemia.

aHCO3- is also severely low, indicating a primary metabolic acidosis.

pCO2 is low, indicating respiratory compensation.

AG (125 - (100+8)) = 17, anion gap metabolic acidosis

Expected pCO2 = 18-22 mmHg,

measured pCO2 is higher than this, thus there is a coexisting respiratory acidosis, likely due to a respiratory infection causing dyspnea + i_nsufficient compensation_ of the primary acidosis.

Corrected HCO3- = 13 mM, since < 22mM there is an additional metabolic acidosis.

Conclusion:

Primary anion gap metabolic acidosis with coexisting respiratory - and metabolic acidosis.

Rigors can be explained by hypokalemia, or simply by chills and fever associated with infection.

Question 38

1. A person fainted while working in the summer heat for a long time.

Complaints:

thirst,
dry mouth,
weakness,
oliguria.

Physical examination:

decreased skin turgor

blood pressure: 110/70 mmHg.

Laboratory parameters:

• se [Na+]: 152 mmol/l
• se [K+]: 5 mmol/l
• hematocrit: 0.45
• HGB: 160 g/l
• MCV: 70 fl

How do you explain the laboratory parameters? What is to be done with the patient?

Answer 38

Fainting in the summer heat suggests heat exhaustion. The complaints and physical findings fit with severe dehydration.

Diagnosis: Hypernatremic Hypovolemia due to Heat Exhaustion

Slightly low blood pressure (normal is 120-130/80-85 mmHg) is sign of hypovolemia

Hypernatremia (normal is 135-145 mmol/l)

A common mistake is that sweat is hypertonic because it tastes salty, but it is actually hyposmotic because most of the Na+ is reabsorbed in the sweat ducts. And since the fluid lost is hyposmotic, the remaining fluid in the body will be hyperosmotic/hypernatremic.

Potassium is high-normal (normal is 3.5-5 mmol/l): also indicates more fluid loss than electrolyte loss

Normal hematocrit (f: 0.37–0.47, m: 0.40–0.54),

normal hemoglobin (f: 120–165 g/l, m: 135–170 g/l): this rules out blood loss as a cause of for the hypovolemia

Microcytosis (MCV normal is 80–95 fl)

• H2O is pulled out of the cells by osmolar forces, leading to cellular dehydration.

Treatment:

Cooling (remove from hot environment, ice packs near groin and axilla)

Lay patient down supine or in Trendelenburg position (feet elevated) to ensure perfusion to brain, prevent further fainting

Oral water replacement (hypotonic fluid) or IV H2O (5% glucose solution) if she’s still unconscious.

• 5% glucose is an isosmotic solution which will slowly restore balance. Normal saline (0.9% NaCl) should not be used because the patient is hypernatremic.

Question 39

2. An elderly person gets sick while enjoying himself on Oktoberfest: he complains of a headache and muscle cramps. He is disoriented. He has drunk 4 liters of beer during the past 2 hours.

Physical examination:

alcoholic breath,

increased plantar extensor reflex.

Blood pressure: 180/100 mmHg.

Laboratory parameters:

• the [Na +]: 126 mmol / l
• se [K+]: 4 mmol/l
• MCV: 102 fl
• hematocrit: 0.36
• se [creatinine]: 150 μmol/l
• se [urea]: 18 mmol/l
• urine: density: 1.015 kg/l; [Na+]: 20 mmol/l

How do you explain the symptoms and the laboratory results?

Answer 39

It is normal to lose kidney function with age, and with this patient being “elderly”, we can assume a reduced GFR. It can be as low as 40-60 ml/min (normal is 120 ml/min)

Beer is a hypotonic solution with some alcohol, and max recommended fluid intake is 1.2 L/hour in healthy adults, less in elderly (kidney excretion rate).

The patient has drunk 2 L/hour, which resulted in water poisoning (hyponatremic hypervolemia), especially with the reduced GFR.

Acute water poisoning with se[Na+] > 120 mmol/l leads to brain edema.

This seems to already have started in this man, considering complaints and plantar extensor/Babinski reflex (sign of increased intracranial pressure).

BP is high (normal 120-130/80-85 mmHg) is because of hypervolemia.
[Na+] is reaching critically low levels (normal is 135-145 mmol/l) .

We should expect hyperkalemia because of the decreased kidney function, however it might be masked by dilution (normal is 3.5-5 mmol/l).

He has macrocytic RBCs because the osmolar forces are pulling water into the cells (normal MCV is 80–95 fl)

Hematocrit appears low because of dilution by the hypervolemia, this is most probably not anemia (normal htc is 0.40–0.54 in males)

High serum creatinine and urea levels (azotemia) indicate renal failure.

(normal cr is 40–130, normal urea is 3.5–7.0)

His urine density is within the normal range (1.010–1.035), however, with water poisoning we should expect a lower urine density, closer to water, so his density being in the normal range actually indicates insufficient kidney function, he cannot dilute his urine enough.

Increased sodium in the urine is another sign of insufficient kidney function
(normal is <20 mmol/l).

Diagnosis:
A healthy person would probably have been able to handle this amount of fluid/alcohol, however, as you get older your kidney function decreases, resulting in a markedly reduced GFR.

This patient suffers from water poisoning from drinking too much and having age-related renal failure.

**Treatment:

IV Mannitol**

(a non-metabolizable osmotically active solution that will pull water out of his cells). He may also need dialysis.

Question 40

3. An elderly woman has been on NSAID treatment for a long time, because of her rheumatoid arthritis. She got very weak after having an acute diarrhea; she feels too dizzy and needs to sit down.

Physical examination:

decreased skin turgor.

Blood pressure in the

• supine position: 120/80 mmHg,
• standing: 90/55 mmHg.

Laboratory parameters:

the [Na +]: 116 mmol / l

se [K+]: 6.2 mmol/l

Ht: 0.48

se [creatinine]: 180 μmol/l se [urea]: 18 mmol/l

urine: [Na+]: 50 mmol/l.

How do you explain the symptoms and the laboratory results?

Answer 40

Probable Cause: Hypovolemic Hyponatremia due to renal failure and diarrhea

Diarrhea → hypovolemia →general sympathetic redistribution of blood→hypoperfusion of kidney→low GFR → release of renin → angiotensin II → more constriction in afferent arteriole of glomerulus

NSAID comes into play→ no PGE → not only afferent, also vasa recta constriction → medullary hypoxia → tubular lesions → no reabsorbtion of Na+ and excretion of K+.

This effect is called analgesic nephropathy or phenacetin nephropathy

The kidney failure explains increased sodium excretion and potassium retention.

The diarrhea is a cause of dehydration that can also worsen the electrolyte abnormalities.

Orthostatic hypotension due to hypovolemia. Explains dizziness, needing to sit down. (normal BP is 120-130/80-85 mmHg)

Hyponatremia: related to high urinary sodium excretion (normal is 135-145 mmol/l)

High urinary sodium: a sign of renal failure, inability to perform normal sodium reabsorption (normal is <20 mmol/l)

Hyperkalemia: normal for renal failure due to decreased urinary excretion of K+ (normal is 3.5-5 mmol/l)

High hematocrit: due to hypovolemia (normal is 0.37–0.47 for females)

High serum creatinine and urea (azotemia): indicates renal failure

(normal cr is 40–130, normal urea is 3.5–7.0)

Note that overdose of NSAIDS also causes acute tubular necrosis (ATN)

Decreased skin turgor: when pulled, the skin takes an abnormally long time to return back to normal shape. This is a typical sign of dehydration.

Question 41

4. How will the following laboratory values be changed in a protracted, untreated diabetic ketoacidotic coma before treatment?
   - total potassium of the body
   - total sodium of the body
   - total water (fluid) of the body.

Does the serum potassium concentration change in parallel with the total potassium amount of the body?

How do you think the appropriate treatment will change the serum potassium concentration?

Answer 41

DKA is an acidosis caused by the presence of excessive ketoacids produced because of the body’s inability to use glucose. It usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counterregulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine).

DKA is treated with fluids, electrolytes — such as sodium, potassium and chloride — and insulin. Perhaps surprisingly, the most common complications of diabetic ketoacidosis are related to this lifesaving treatment.

Total potassium of the body

Potassium exists mostly in the IC compartments of the body (97%), however, in an acidemia the potassium is exchanged for protons, and pulled out of the cells.

Additionally there is probably a hyperkalemia (explained below), which means that there is more potassium to be lost.

Then, a lot of this serum potassium is lost into the urine because of osmotic diuresis, remember that the pumps in the tubules reabsorbing electrolytes not only rely on concentration gradients, but also charge gradients.

For these reasons, Total Potassium of the body is decreased

Total sodium of the body

Sodium exists mostly in the EC compartments of the body (90%)

Thus we expect massive sodium loss due to osmotic diuresis, way past the kidney’s ability to reabsorb

Total water (fluid) of the body

Around ⅔ of our water is IC, ⅓ is EC.

Massive water loss due to osmotic diuresis, ketones and glucose have a huge osmotic pull, and will pull the water out of the cells, the kidneys won’t be able to keep up, and it will be lost in the urine.

We expect cellular dehydration and microcytosis (MCV > 80 fl)

Does the serum potassium concentration change in parallel with the total potassium amount of the body?

No, they do not change in parallel. This is explained by three events:

Firstly, water loss is greater than potassium loss, and so hyperkalemia develops.

Secondly, the kidneys are trying to combat the acidemia by extracting protons from the serum, in exchange for potassium (H+/K+ exchanger), and so hyperkalemia develops

Thirdly, absence of insulin means that the Na+/K+ ATPase is inadequately stimulated, and so more K+ is left in the serum and not retained intracellularly.

• This is important to keep in mind for treatment, when insulin is given it will rapidly deplete the extracellular potassium, causing a transient hypokalemia.

How do you think the appropriate treatment will change the serum potassium concentration?

Tx of DKA:

Dialysis: This case is very severe, we need to work fast

Calcium-gluconate to antagonize the hyperkalemia in the cardiomyocytes and prevent fibrillations

(Calcium-gluconate prevents K+ from entering the cardiomyocytes, without affecting serum K+-levels)

Insulin
Lack of insulin is the cause of DKA. Insulin draws glucose into the cells, correcting both the hyperglycemia and the cell starvation that causes ketone production/acidosis. We also need to observe glucose-levels to prevent insulin-induced hypoglycemia

Insulin will restore the Na+/K+ ATPase activity, pumping K into the cells and removing it from the extracellular space. Additionally, the total body potassium is reduced due to the osmotic diuresis. Thus, hypokalemia can rapidly develop as fluids are replaced and insulin stimulates the Na+/K+ ATPase. (note the main risk of hypokalemia is respiratory muscle paralysis)

Correction of fluid loss with intravenous fluids (Lactated Ringers solution)

Slow, or intermittent infusion of K+ will almost certainly need to be used, monitoring K+-levels during the treatment is extremely important

Correction of acid-base balance with bicarbonate

This treatment is extremely complex due to the intricacies of the body’s own homeostatic systems. Potassium is one of the primary issues, as its concentration in the serum needs to be kept within a very narrow range due to arrhythmias etc. According to the department, the preferred order of treatment is

first fluid + electrolytes (via lactated Ringer’s),
then insulin (slowly),
then K+

Question 42

5. An elderly man gets chemotherapy for his chronic lymphoid leukemia. He complains of intermittent palpitation, and being disoriented.

Blood pressure: 90/60 mmHg.

Laboratory parameters:

the [Na +]: 130 mmol / l

se [K+]: 8.2 mmol/l

hematocrit: 0.28

How can you explain these laboratory results? What kind of ECG-abnormalities you expect to see? What would you do with him?

Answer 42

Sodium is within normal range (135-145 mmol/l)

The high serum potassium is a result of massive cell lysis from the chemo, which also causes the palpitations (normal is 3.5-5 mmol/l).

We have too little information to fully explain the hypotension, but probably from either arrhythmias or from cardiotoxicity of the chemotherapy
(normal BP is 120-130/80-85 mmHg)

Low hematocrit:

low RBC production due to bone marrow “overpopulation” from the malignancy, and additionally from bone marrow destruction from the chemotherapy (normal htc for males is 0.40–0.54).

Should request HGB (should be low) and MCV(should be microcytic) to confirm anemia of chronic disease.

• *Disorientation** due to low blood pressure and low blood supply to the brain.
• —————————————————————————————————————————What kind of ECG-abnormalities you expect to see?

Hyperkalemia will change the T wave: high amplitude and tent-like in most leads. QT interval is prolonged. The QRS complex may be wider. This state is susceptible for Vfib (“R on T”).

• *Palpitations** are felt due to arrhythmias from hyperkalemia

What would you do with him?

Dialysis

Treat hyperkalemia:

• First and foremost we need to stabilize the myocardium using IV Calcium-gluconate, which antagonizes the hyperkalemia.
• We can use insulin to activate the Na+/K+ ATPase and move the potassium intracellularly, also needs glucose to prevent hypoglycemia
• When his blood pressure and serum potassium levels normalize, we can start inducing renal excretion of potassium with a thiazide (inhibits Na+/Cl- antiporter) or furosemide (inhibits Na/2Cl/K symporter) diuretic.

Treat hypotension and low hematocrit:

• We need to elevate the blood pressure using IV saline
  (and maybe beta agonists?)
• Hematocrit may be corrected with blood transfusion

second this - colloid IV is enough

Question 43

6. A woman gets hospitalized after having broken several of her bones in a car accident. Blood pressure: 80/50 mmHg, HR: 130/min. The patient develops oliguria after being stabilized.

Laboratory parameters (later):

se [Na+]: 150 mmol/l

se [K+]: 7.2 mmol/l

se [creatinine]: 250 μmol/l

se [urea]: 18.8 mmol/l

hematocrit: 0.33

Urine amount (by catheterization): 200 ml

What emergency treatment is necessary? How can you explain the parameters seen later?

Answer 43

Her blood pressure is low (normal is 120-130/80-85 mmHg) and she is tachycardic (normal HR is 60-100)

Patient had circulatory shock due to the trauma with likely significant internal hemorrhage. There is high risk of MOF (Multi-Organ Failure), with significant renal damage.

The emergency treatment is the following:

Stop any bleedings etc (ABC)

Restore the blood pressure with **IV Dextran

dialysis, calcium-gluconate and insulin**

(Unsure whether starting dialysis is part of the emergency treatment, but you would definitely start dialysis immediately when you see her labs)

How can you explain the parameters seen later?

From the lab values we can tell that her potassium is way too high (normal is 3.5-5), we need to stabilize her heart with Calcium-gluconate, and move potassium into her cells with insulin. When giving insulin you need to be wary of hypoglycemia.

Her lab values are all signs of acute kidney failure:
Oliguria (on borderline of anuria, which is < 200 mL/day) (normal is 1-1.5 L)

• Her urine output should be increased, give IV Mannitol, and continue dialysis

Elevated sodium (normal is 135-145 mmol/l) - can be explained by renal hypoperfusion → decreased GFR → RAAS → Aldosterone action to try and increase blood pressure.

Elevated potassium because of trauma/necrosis and also kidney failure (normal is 3.5-5 mmol/l)

Elevated serum creatinine and urea (azotemia) (normal cr is 40–130, normal urea is 3.5–7.0) is a clear sign of acute renal failure .Kidneys get so little blood that kidney cells can die → oliguria. Usually tubular cells die in case of anoxia → Acute tubular necrosis.

Hematocrit is low because of the bleeding from the trauma, that has not been corrected by a blood transfusion (normal for females is 0.37–0.47)[2]

Retention parameters:

all are increased → suggest renal insufficency

Kidney regenerate: can become healthy, depending on the extent of the renal damage. If function does not come back, transplantation is needed, this is better than chronic dialysis.

Emergency treatment:
o Fluid replacement :IV DEXTRAN increase renal blood flow
o Ultrasound: check organs
o Oxygen
o Pain killers
o antibiotics