Cases Semester II

Question 1

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 1

• 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 2

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 2

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 3

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 3

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 4

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 4

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 5

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 5

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 6

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 6

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 7

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 7

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 8

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 8

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 9

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 9

• 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 10

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 10

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 11

1. A 56-year-old woman complains of fatigue. According to her medical records, she has hypertension, peptic ulcer and nephrolithiasis.

Laboratory findings:

serum Ca: 2.8 mmol/l
serum phosphate: 0.6 mmol/l
serum ALP: 450 U/l
DEXA scan: T-score of –2.8 SD on the hip and forearm.

What test(s) would you order to determine the exact cause of her disease?

Answer 11

Elevated serum [Ca2+] (normal: 2.2-2.6 mmol/L)

• High serum calcium can be cause of nephrolithiasis (kidney stones) and fatigue

Low serum [Pi] (normal: 0.8-1.45 mmol/L, although it’s not listed on the lab values sheet)

Elevated serum ALP (normal: < 150 U/L)

• In this situation, high ALP probably indicates increased osteoblast activity

ALP is usually normal in people with primary osteoporosis, and so this is an indicator that here there is a problem with hyperparathyroidism ⇨ osteoclast bone resorption ↑

Osteoporotic T score (normal > -1.0, low bone mass/osteopenia if -1.0 to -2.5, osteoporosis if < -2.5)

T score is the patient’s bone density compared (by standard deviation) to the bone density of a young population (30 years old). It is measured by DEXA: Dual Energy X-ray Absorptiometry

Probable Diagnosis: Primary Hyperparathyroidism

(intrinsic oversecretion of PTH from parathyroid gland. Can be caused by adenoma or hyperplasia) Osteoporosis because of PTH ⇨ osteoclast activity ↑, bone resorption ↑

• Note that this is secondary osteoporosis, because osteoporosis is only “primary” if it’s the common postmenopausal, age-dependent kind

PTH increases osteoclast activity ⇨ Ca2+ ↑

PTH induces increased production of vitamin D + induces kidney to increase calcium reabsorption and phosphate excretion ⇨ [Ca2+] ↑↑, [Pi] ↓

Hypercalcemia frequently induces increased gastrin secretion that may cause hyperacidity and thus be the cause of the peptic ulcer

(Gastrin stimulates parietal cells to secrete more HCl)

Additional tests to determine disease:

Scintigraphy with 99mTc to check parathyroid function,

imaging for neoplasia

Ultrasound: can be done, but less specific than scintigraphy

PTH and Vitamin D levels

Biopsy

Question 12

2. A 68-year-old nonsmoking man has been complaining of progressive weakness for 2 weeks.

In addition to these symptoms he has developed intermittent cough, pleuritic chest pain and exertional dyspnea for 6 days. In the last weeks he frequently experienced nausea and vomited several times.

Medical history reveals no hypertension or coronary artery disease.

He has a long history of heartburn – he takes regularly antacids and drinks 1–2 L milk a day.

Laboratory findings:

serum Ca: 2.8 mmol/l
serum phosphate: 1.8 mmol/l
BUN: 24 mmol/l
HCO3-: 38 mmol/l
PTH and vitamin D: normal.

What is the most likely diagnosis?

Answer 12

Probable Diagnosis: Milk-Alkali Syndrome:

the chronic ingestion of high amount of antacids and milk + hypercalcemia are strong clues

Hypercalcemia: (normal 2.2-2.6 mmol/L)

• Ingestion of too much bicarbonate (and its negative charges) leads to corresponding absorbance of positively charged calcium
• Hypercalcemia can have a CNS-depressing effect, this leads to autonomic dysfunction that causes GI symptoms (nausea + vomiting) as well as explaining the progressive weakness the patient is experiencing

Hyperphosphatemia: (normal 0.8-1.45 mmol/L): sign of renal failure

High BUN: (normal 2-10 mmol/L)

• Chronic milk alkali syndrome leads to kidney failure via nephrocalcinosis

High bicarbonate: (normal 21-26 mmol/L)

• Over-absorption of bicarbonate causes the person to have mild alkalosis

Pleuritic chest pain, dyspnea, cough: hypercalcemia may have made ectopic calcifications of the lungs

PTH and Vitamin D normal: rules out other potential causes, like hyperparathyroidism

Question 13

3. A 35-year-old woman is complaining about frequent muscle cramps. She was admitted to the hospital after having a convulsion.(sudden movement of the body)

She had thyroidectomy 3 months ago and she is on thyroid hormone substitution since then.

Physical examination revealed a positive Chvostek’s sign and Trousseau’s phenomenon.

Laboratory findings:

serum Ca: 1 mmol/l
serum phosphate: 2.0 mmol/l
serum ALP 140 U/l

What is your diagnosis? What further test(s) would you order to support your diagnosis?

Answer 13

Diagnosis: PTH Deficiency due to Thyroidectomy where the parathyroid glands were also lost in the surgery

Severe hypocalcemia: (normal 2.2-2.6 mmol/L) - this is a life-threatening level; she is at risk of laryngeal spasm that could occlude her airway

Hypocalcemia causes hyperexcitability of the muscles, leading to symptoms of muscle cramping, convulsion,

Chvostek sign: touch the masseter muscle ⇨ twitching

Trousseau’s phenomenon: inflate blood pressure cuff ⇨ flexor muscles in hand and forearm contract/spasm.

(not to be confused for Trousseau’s other phenomenon: migratory thrombophlebitis)

Hyperphosphatemia: (normal 0.8-1.45 mmol/L)

• PTH normally stimulates phosphate excretion. Without PTH ⇨ serum [Pi] ↑

Normal ALP: ( < 150 U/L)

Further Tests:

PTH levels: see if there is any endogenous production left

Imaging: maybe do scintigraphy to see if there is any uptake

(May also check for vitamin D deficiency, since PTH stimulates vitamin D synthesis via 1-α OHase stimulation; PTH supplementation would probably fix this, so testing is not entirely necessary)

Question 14

4. A 66-year-old woman felt a sharp, sudden lumbar pain as she was lifting a bag of groceries out of the supermarket cart.

An X-ray taken in the emergency department showed a compression fracture of L1 vertebra.

Laboratory findings:

serum Ca: 2.4 mmol/l
serum phosphate: 1.1 mmol/l

What is your diagnosis? What further tests would you order?

Answer 14

Diagnosis: Pathological Fracture - fracture during normal activity, likely due to Primary(postmenopausal) Osteoporosis

This person is very likely to have osteoporosis based on pathological fracture + demographics of 66 year old woman (postmenopausal, primary osteoporosis)

Estrogen stimulates OPG production, and OPG decreases osteoclast activity.

After menopause, low estrogen ⇨ overactive osteoclasts ⇨ extensive bone remodeling / osteoporosis

Normocalcemia (2.2-2.6 mmol/L) and Normophosphatemia (0.8-1.45 mmol/L) are both typical of primary osteoporosis, and rule out other causes:

If she had osteomalacia, Ca and Pi would probably be low

If she had hyperparathyroidism, Ca would be high and Pi could be low or high, depending on the origin of hyperparathyroidism

Further tests:

DEXA: see her T score to diagnose osteoporosis

Possibly additional labs: PTH, ALP, urinary calcium and phosphate. All should be normal.

Maybe check estrogen levels

Question 15

5. A 60-year-old diabetic woman has been on hemodialysis for 15 years. She recently started to complain of cardiac pain.
   She has no history of cardiac illness.

Physical examination reveals pale, grey-yellow colored skin, but nothing else remarkable.

Exercise electrocardiogram shows ST-T alterations.

Laboratory findings:

ALAT: 45 U / l
ASAT: 52 U / L
ALP 120 U / l

Serum creatinine: 180 mmol / l

Serum Ca: 2.1 mmol / l

serum phosphate: 2.8 mmol/l

serum PTH: elevated

What is the possible diagnosis?? What further tests would you perform?

Answer 15

Possible Diagnosis: Renal Failure with Secondary Hyperparathyroidism

Several Known Mechanisms:

• Damaged kidney cannot remove enough phosphate ⇨ hyperphosphatemia ⇨ Pi binds to free Ca2+ ⇨ free [Ca2+] ↓ ⇨ stimulation of PTH secretion
• Damaged kidney has poor enzymatic conversion of vitamin D (1α-hydroxylase) ⇨ low vitamin D ⇨ reduced Ca2+ absorption ⇨ hypocalcemia ⇨ stimulation of PTH secretion
• High Pi levels stimulate osteoclasts to secrete FGF-23 ⇨ vitamin D synthesis inhibited ⇨ reduced Ca2+ absorption ⇨ hypocalcemia ⇨ stimulation of PTH secretion (FGF-23 also more directly stimulates PTH secretion)

Normal ALAT (normal < 45 U/L) - liver is fine

Slightly elevated ASAT (normal < 45 U/L)

• ASAT is also present in organs like the kidneys and heart, and the increased ASAT here could be relevant to either of these

Normal ALP (normal < 150 U/L)

High serum creatinine (normal 40-130 µmol/L)

• Indicates low GFR, poor kidney function

Slightly low calcium (normal 2.2-2.6 mmol/L)

• Due to mechanisms described earlier

High phosphate (normal 0.8-1.45 mmol/L)

• Due to renal failure with decreased renal excretion of Pi. High Pi leads to decreased vitamin D synthesis and increased PTH secretion

Elevated PTH indicates hyperparathyroidism

Cardiac pain and ST-T changes

These two signs indicate problems with repolarization, probably due to insufficient oxygenation. There is probably some macroangiopathy/ atherosclerosis due to diabetes and secondary hyperparathyroidism. She is also anemic, which worsens oxygenation. (Thanks Fredrik)

Note also the patient is at risk for arrhythmias from electrolyte disturbances:

Hyperkalemia is a common problem with chronic renal failure,

• and has a strong risk for V-fib.

Hypocalcemia can also cause cardiac/ECG changes (in particular QT prolongation), but I doubt the calcium level here is low enough to have that effect.

• The main risk of long QT interval is Torsade de Pointes.

Paleness may be related to anemia due to decreased EPO production with chronic renal failure. Gray-yellow skin also can be the result of severe chronic kidney failure.

What further tests would you perform?

Should perform many tests due to complicated effects of kidney disease

Rule out AMI by cardiac enzymes: Troponin T, CKMB, LDH1.

Ultrasound and/or Scintigraphy with 99mTc. Imaging for parathyroid gland hyperplasia

Other serum electrolytes: especially K+, but also Na+ and Cl-

Vitamin D levels: probably low

Related kidney diagnostics: BUN, creatinine clearance, urine volume, etc.

Blood glucose level, check for glucosuria

In Renal osteodystrophy, involves hyperparathyroidism and loss of bone mass (overactivation of osteoclasts -> Ca2+ is reabsorbed and lost by the kidney)

Consider DEXA

Treatment: VitD + calcium supplements

Note that if a patient goes with an untreated secondary hyperparathyroidism for too long (several years) he/she can develop a tertiary hyperparathyroidism. This means development of autonomous PTH secretion (Tornóci called it adenoma) that stays high even after treatment is applied.

Question 16

6. A 65-year-old man complains of frequent urination and urinary retention. There is no macrosopic hematuria, urination is not painful. He complains of recurrent abdominal pain in the last weeks.

Laboratory findings:
serum Ca: 3.5 mmol/l

serum phosphate: 2 mmol/l

BUN: normal

What is the possible diagnosis? What further tests would you perform to support your diagnosis?

Answer 16

Possible Diagnosis: Prostate Carcinoma with Bone Metastases

Prostate cancer frequently metastasizes to the vertebrae, where it can form Osteolytic bone lesions that (rarely) cause hypercalcemia and hyperphosphatemia

Bone metastases are more commonly “blastic” (bone-forming), inducing a cycle in which increased PTH→ causes bone resorption from other sites while increased PTH1-R expression on metastatic cells stimulates their growth and subsequent nearby bone formation.

Our department likes to hear about the osteolytic lesions as the source of hypercalcemia, but this is not all there is to it, and to me this explanation is more interesting and complete… sorry. (Ben). YALLLA YA FALTSANNN

Urinary retention and frequent urination + older male + no bleeding + no pain on urination all suggest that the prostate is enlarged.

Severe hypercalcemia (normal 2.2-2.6 mmol/L) - this is an alarmingly high level; he is at risk for cardiac arrest/coma. In hypercalcemia, calcium ions block the NMJ sodium channels, making muscle cells less excitable.

• Recurrent abdominal pain symptoms could be related to hypercalcemia causing loss of tonicity of the bowels and constipation. Could also be a peptic ulcer.

Elevated phosphate levels: (normal 0.8-1.45 mmol/L)

• Like elevated calcium, this can occur from neoplastic bone lesions

Having both elevated calcium and elevated phosphate levels shows that kidney disease is not the source of his problem

Normal BUN: despite urinary retention, kidney function seems OK

Further tests:

Prostate evaluation:
digital-rectal,
biopsy,
PSA
(although not specific nor sensitive for diagnostics; according to Molnar it is the bound form of PSA that is measured)

Imaging of Metastases:
CT,
X-ray,
MRI

ALP: may be elevated with bone destruction

PTH: due to the above-mentioned mechanism; suppression of serum PTH levels may help limit growth of PTH1R+ metastases (again, this is extra)

Question 17

1. What laboratory tests would you perform in case of an upper respiratory inflammatory disease accompanied with fever?

Mention a few positive/negative acute phase proteins!

Answer 17

Obtain Specimen / Make Culture: see if it’s streptococcus, viral etc.

WBC count: Normal range: 4-10 G/L

• Can suggest if infection is bacterial (neutrophils ↑) or viral (lymphocytes ↑)

Erythrocyte Sedimentation Rate (ESR): normal is < 20 mm/hour.

Non-specific marker of inflammation.

• Usually increases during inflammation due to increased production of acute phase proteins like fibrinogen, which is a large molecule that causes erythrocytes to stick together better, increasing their rate of sedimentation.
• ​Women tend to have higher ESR due to lower hematocrit as a result of menstrual bleeding

Technically, ESR should be between 2 and 10 mm/hour for men, and 20 mm/hour for women, but this is not on the lab diagnostic values sheet.
ESR > 100 mm/hour is an indicator of sepsis, pneumonia, and plasmacytoma

CRP: normal range: 1-8 mg/L

• CRP is a positive acute phase protein, increasing 100-1000x in acute inflammation.

*Note that very slight elevations in CRP within diagnostic “normal range” (3-8 mg/L) are used to measure chronic inflammation, and they are strong indications of risk for heart attack or stroke. The 1-8 range is only for checking for acute inflammation.

Procalcitonin: increases in severe bacterial, fungal, and parasitic infections

More specific than CRP

Serum Protein Electrophoresis: during inflammation, normally see: Albumin ↓ while Gamma globulins ↑

(described as A/G ratio ↓, which is a value we have to remember. Normal: 1.25-2.5)

Gamma range ↑ with IgG, IgA, IgM increases depending on the phase/type of infection

Positive Acute Phase Proteins: levels increase during inflammation

CRP: binds some bacteria and induces the complement cascade

• *S**erum Amyloid A: similar function to CRP. In chronic inflammation, may misfold and ⇨
• *amyloidosis**

Fibrinogen: clumps bacteria together

Ceruloplasmin: scavenges oxygen radicals generated by leukocytes

Protease inhibitors: α1-antitrypsin, α2-macroglobulin

Haptoglobin: binds globin in plasma for recycling, inhibiting microbe iron uptake

Complement factors: opsonize, perform chemoattraction signaling, MAC

Hepcidin: prevents uptake of iron (in chronic inflammation, this high hepcidin level can cause anemia)

Negative Acute Phase Proteins: levels decrease during inflammation

Transferrin:
bacteria need iron to grow, and inhibiting transferrin deprives them of an iron source

Albumin:
decreases to save amino acids for positive APP production and to prevent hyperproteinemia

Normal plasma protein values:

Total protein: 60-80 g/L

Albumin: 35-50 g/L

A/G ratio: 1.25-2.5

CRP: 1-8 mg/L

Question 18

2. What is the significance of an elevated ESR?

Answer 18

Erythrocyte Sedimentation Rate (ESR) is traditionally measured in a thin Westergren tube (nowadays it’s automated). Blood is allowed to sit in the tube for one hour, and the red blood cells settle (“sediment”) at the bottom of the tube at a variable rate measured in mm/hour. Depends on many factors.

The red blood cells are negatively charged, which have a repelling effect on each other. This effect is called the “zeta potential,” and it normally slows down the rate at which erythrocytes sediment.

Causes of Elevated ESR:

Anemias: due to lack of red blood cells, the zeta potential is reduced, allowing erythrocytes to settle faster (Zeta Potential ↓ = ESR ↑)

Pregnancy: erythrocyte sedimentation rate increases during pregnancy due to an increase in fibrinogen and globulin levels; there is however a fall in the amount of albumin

Some malignancies: such as lymphoma or multiple myeloma

Hypoalbuminemia:
albumin is also negatively-charged, and its large presence in the serum contributes to the repellant effect of RBCs. Without albumin, there is a lower negative repellant effect, and so RBCs settle faster ⇨ ESR ↑

Hypoalbuminemia usually is the result of liver or kidney failure

Inflammation:

fibrinogen is produced in large quantities in inflammation, and fibrinogen is a large protein that helps RBCs to clump faster ⇨ ESR ↑

• Similar effect occurs from hypergammaglobulinemia

ESR is measured in millimeters of sedimented RBCs / hour.

Males: 2-10 mm/hour

Females: 2-20 mm/hour

Women are more likely to have higher ESR due to comparatively lower hematocrit due to menstrual bleeding. Same mechanism as anemia but not severe enough to be pathological

Question 19

3. A 54-year male patient complains of dysuria. He voids frequently, but little amount.

The laboratory tests show an elevated PSA value.

What may be the cause of the symptoms and the laboratory result?

What other tests would you perform?

Answer 19

Prostate Specific Antigen (PSA) is a tumor marker for a product of prostate cells. Tumor markers are not specific (people without prostate cancer may have the marker) nor sensitive (people with prostate cancer may not have the marker).

In general, tumor markers are better for follow-up after treatment than for the initial diagnosis. Elevated tumor markers hints at a problem, but it is not enough for diagnosis alone.

Possible causes:

Benign Prostate Hyperplasia:

does not indicate cancer risk, but prostate hyperplasia typically occurs as men age. The whole prostate undergoes hyperplasia and obstructs the urethra, causing dysuria.

PSA can be elevated with BPH as well as prostate carcinoma

Prostate Carcinoma:

Usually does not obstruct the urethra until later in the tumor progression

(most common location for the tumor is in the posterior lobe, and is usually peripheral, but can grow centrally)

This is the main concern for high PSA levels

Prostatitis:

inflammation of prostate. PSA should not be elevated as a result of prostatitis, but it could be a false positive.

Additional tests:

Digital-Rectal examination: normal screening for older men. Can palpate neoplastic growth on prostate.

General inflammatory markers (CRP, WBC count, etc.) to check for prostatitis

Biopsy: best way to know for sure if it’s carcinoma

If prostate carcinoma is confirmed, check for metastases, especially vertebral metastases (typical of prostate carcinoma due to pattern of venous drainage).

X-ray,
CT,
MRI.
Check ALP.

Question 20

4. What would be the characteristics of an ideal tumor marker?

Answer 20

Ideal tumor markers:

Specific and sensitive marker of the tumor

For proper screening, both sensitivity and specificity should be > 95%

Sensitivity: those who have the disease have the marker

Specificity: those who are not sick do not have the marker

Tumor marker levels should correspond to tumor growth to give you an estimate of the size

Tumor marker levels should still be detectable even with tiny and early-stage neoplasms

Practical reasons: cheap, easy, accessible, fast

Level should change in response to tumor size

An abnormal level should be obtained in the presence of micrometastases

The level should not have large fluctuations that are independent of the changes in tumor size

Levels in healthy individuals are at much lower concentrations than those found in cancer patients.

Predict recurrences before they are clinically detectable.

Test should be cost effective.

No marker are 100% ideal.

Question 21

5. A middle aged hemophiliac patient, who has had numerous blood transfusions before, is admitted to a hospital, to drain her huge ascites.

The laboratory tests show an elevated AFP level.

Laparoscopy performed at the time of draining the ascites fluid revealed several large solid lesions in the liver. What is a likely explanation of these findings?

Answer 21

AFP (alpha-fetoprotein):

α-fetoprotein (AFP) is normally produced by the embryonic liver as a substitute for albumin. In hepatocellular carcinoma, this fetal form of albumin is often produced again. This could explain the liver lesions[1] .

Numerous blood transfusions ⇨ increased risk for viral hepatitis (at least before they started screening for hepatitis C in the 90s). Hepatitis C ⇨ risk of transformation to hepatocellular carcinoma

However, with multiple liver lesions, metastases are a more likely explanation. Most GI cancers frequently spread to the liver, but colon cancer is the most common by prevalence and so it’s one to examine as a possibility first. Needs biopsy and more imaging.(Thanks Priyanka)

Ascites mechanisms:

Liver damage ⇨ portal hypertension ⇨ increased capillary hydrostatic pressure in abdomen that pushes fluid into the peritoneal cavity

Impaired liver function ⇨ hypoalbuminemia ⇨ decreased colloid osmotic pressure ⇨ edema formation

Edema ⇨ Low fluid volume in the vasculature ⇨ Renin-Angiotensin-Aldosterone system activated ⇨ retention of sodium and water ⇨ diluted, protein-deprived blood is more prone to edema formation

Chronic hepatitis can cause hepatocellular carcinoma directly
or
through causing cirrhosis, → may cause cancer.

Another possibility:

pregnancy AFP is elevated. It is measured in pregnant women through the analysis of maternal blood or amniotic fluid as a screening test:

• Increased in open neural tube defects and omphalocele
• Decreased in Down syndrome

—————————————————————————————————

Question 22

6. The plasma AFP level was found to be abnormal on screening a pregnant woman.

What do you think this means, and what other tests should be done?

What is the significance of an abnormal AFP level in a man or non-pregnant woman?

Answer 22

Pregnant Women:

With pregnant women, AFP is used as a diagnostic marker of fetal development.

[Please note that AFP is taken less seriously because of false-positives, ultrasound is better for diagnosis]

High AFP can indicate:

Twins (twice the baby, twice the AFP)

Problem with neural tube closure (e.g. spina bifida, anencephaly,omphalocele) ⇨ increased AFP leakage

• Neural tube defects are strongly correlated with folate deficiency

Low AFP can indicate:

Intrauterine fetal death

Down syndrome

Men and Non-Pregnant Women:

AFP is the fetal form of albumin, and certain neoplasms produce it.

AFP is commonly produced in hepatocellular carcinoma, and in testicular or ovarian cancer.

AFP is used as a tumor marker for people who aren’t pregnant. Like other tumor markers, it should not be used alone for diagnosis, but can be used for prognosis.

Question 23

7. Evaluation of the plasma proteins of a 50-year-old male patient gives the following results:

total serum protein: 90 g/l (N: 60-80 g/l)

A/G quotient: 0.38 (N: 1,5-2,5)

albumin: 27% (30-50 g/L)

globulins:
α1: 4% (normal)
α2 : 6% (normal)
β: 8% (normal)

γ: 55% (↑↑↑)

IgG: 56 g/l (↑)
IgA: 0 g/l (↓)
IgM: 0.6 g/l (↓)

CRP: normal

ESR: 100 mm/h (N. in men: 2-10 mm/h)

serum Ca++: 2.71 mmol/l (N: 2,2-2,6)

uric acid: 708 μmol/l (N: 150-400)

Anti-IgG and anti-kappa antibodies are strongly positive.

What is the most likely diagnosis and what diagnostic procedure would you order?

Answer 23

Likely Diagnosis: Multiple Myeloma or possibly another type of Monoclonal Gammopathy

Multiple Myeloma is a lymphoid neoplasm in which plasma cells continuously produce antibodies, usually IgG, and/or fragments of antibodies such as kappa light chain. The neoplasm normally occurs in the bone marrow, and it displaces healthy bone marrow + makes lytic lesions throughout the skeletal system.

Elevated total serum protein: (normal 60-80 g/L) due to antibodies ↑↑↑

Low Albumin/Globulin Fraction (normal 1.25-2.5) - which is shown again in the remaining values

Relatively low albumin: absolute value is not clear, but the normal value is 35-50 g/L, or ~50-60% of protein content

Very high gamma globulins because IgG ↑↑

Normal CRP: normal 1-8 mg/L

• No immediate infection or inflammation response, so can rule that out as a cause of hypergammaglobulinemia

Very high ESR (normal 2-10 mm/hour)

• Hypergammaglobulinemia typically has an increased ESR, where the immunoglobulins or light chains have asymmetric charges that decrease the zeta potential, allowing RBCs to quickly sediment

Hypercalcemia (normal 2.2-2.6 mmol/L)

• Advanced multiple myeloma classically involves high RANKL production ⇨ increased osteoclast activity ⇨ hypercalcemia

Elevated uric acid: (normal 150-400 µmol/L)

• High cell turnover in multiple myeloma ⇨ uric acid levels ↑
• In multiple myeloma, renal failure frequently occurs due to protein deposition in the tubules, hypercalcemia causing nephrocalcinosis, and misfolded protein deposition in the glomeruli (amyloidosis) therefore your kidneys cannot get rid of the uric acid in your blood

Anti-IgG and anti-kappa antibodies strongly positive:

• Most multiple myelomas produce both IgG and kappa antibodies, which also elevates the ESR

Additional Diagnostics:

Tumor imaging, especially of bone lesions:
CT, MRI, X-ray

Bone marrow biopsy, peripheral blood smear

Assess the crowding-out effect of neoplasm: RBC and WBC counts

Assess renal damage:
BUN,
creatinine clearance,
urinalysis,
kidney biopsy (but probably too invasive) to check for amyloidosis

Question 24

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

Answer 24

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 25

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

pH,

pCO2,

BE,

aHCO3–,

st HCO3–,

AG, se K+

Answer 25

- 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 26

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

Answer 26

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 27

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 27

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 28

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 28

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 29

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 29

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 30

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 30

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 31

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 31

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 32

1) A 46-year-old obese woman has admitted to hospital with subfebrility and malasie. Her right thigh is swollen, with tight skin and dilated superficial veins.

A day ago she started complaining of nausea, sweating, dyspnea and chest pain.

Laboratory data:

RBC: 4,1 T/l (female: 3,8-5,2)

WBC: 13 G/l (normal: 4-10)

PLT: 240 G/l (normal: 150-400)

ESR: 25 mm/h (normal female: 2-20)

LDH: 600 U/l (normal: <160 U/l)

CK: 160 U/l (normal: <200 U/l)

D-dimer: high (>3μg/ml)

AT-3 concentration: 60% of normal

What may cause her symptoms? What tests would you perform to support diagnosis?

Answer 32

WBCs high, indicating inflammation → normal = 4-10 G/l; (platelets + RBCs normal)

ESR high, indicating inflammation → normal < 20 mm/h

LDH high, indicating hemolysis → normal <160 U/l; (CK is normal)

• Extra: high LDH can also indicate many other kinds of tissue breakdown, including those seen in cancer, heart failure, hypothyroidism, anemia, pre-eclampsia, meningitis, encephalitis, acute pancreatitis, HIV and lung or liver disease)

High D-Dimers indicate increased fibrinolysis (are byproducts of fibrin breakdown by plasmin)

Low AT-III indicates active fibrinolysis

• “AT-III” refers to soluble antithrombin in plasma, the form usually discussed.
• In this case, a true deficiency is not seen, but rather a decreased serum level due to the molecule being in heavy use.

​-True antithrombin deficiency can be acquired or inherited:

• Acquired - may be due to
• *1)** increased excretion in renal failure
• *2)** decreased production in liver (cirrhosis, prematurity)
• *3)** accelerated consumption as seen in severe injury
• Inherited
• *Type 1)** decreased AT activity and concentration;
• *Type 2)** normal concentration but reduced activity.

Symptoms are likely caused by deep vein thrombosis leading to pulmonary embolism

• leg edema, LDH, D-dimers and low AT-III indicate DVT
• nausea, sweating, chest pain, dyspnea indicate PE

Chest X-Ray + CT angiography (w/ contrast, shows blocked flow) to check for PE;

Thigh US doppler to look for remains of DVT

Question 33

2) A 45-year-old woman visits her physician for poor health and recurrent fever. She has been troubled by menorrhagia (abnormal heavy and prolonged menstrual period), bleeding after slight traumas and frequent nosebleeds in the last few months.

Her laboratory parameters:

Platelet count: 8 G/l (normal: 150-400 G/l)

Bleeding time: 15 min (normal: 4-6 min)

Prothrombin time: INR = 1,00 (normal: 0,8-1,2)

aPTT: 40 sec (normal: 35-46 sec)

Fibrinogen concentration: 3 g/l (normal: 1,5-4,0 g/l)

What is the possible cause of her bleeding disorder?

Answer 33

Low platelets indicate thrombocytopenia (normal: 150-400 G/l), which can have many etiologies, but most probably acute leukemia

***Molnar: The lowest amount of platelets needed to prevent spontaneous bleeding is 50 G/L

Long bleeding time (normal: 4-6 min) indicates platelet plug formation / endothelium-platelet interaction issues

Prothrombin time by INR is normal (0.8-1.2), indicating no issues with the extrinsic (tissue factor) pathway or common pathway; fibrinogen levels are normal

aPTT is normal (35-45 sec), indicating no issues with the intrinsic pathway
(kallikrein, XII, etc.)

Recurrent fever may indicate an infection as a result of pancytopenia from leukemia

Possible Causes of Thrombocytopenia:

Acute leukemia: most likely cause in this case
Tornoci said this was the correct diagnosis, as indicated by the fever, and that CML would not present as fever

can be via decreased production; increased destruction; medications, etc.
—————————————————————————————————————————-Myeloproliferative Disorders: usually see ↑ cell precursors; ↓ mature platelets

Chronic Myelogenous Leukemia (CML) - Philadelphia chromosome

Essential Thrombocytopenia[1] - JAK2 or MPL (TPO receptor) mutations

Polycythemia Vera - JAK2

Primary Myelofibrosis - JAK2

DIC - via “consumptive coagulopathy”, as platelets are used up throughout the blood in the creation of microthrombi…

In the above case, DIC can probably be ruled out because it tends to prolong PT and aPTT, as it consumes the coagulation factors

Fibrinogen is used up in the coagulative processes of DIC, but it is also synthesized more due to its status as a positive acute phase protein, so fibrinogen levels often look normal in DIC.

Anti-phospholipid Syndrome (APS) - AKA “Hughes syndrome” - can be familial or autoimmune (as in SLE)[2] [3]

numerous antibodies seen in SLE affect platelet function (anti-ApoH/”lupus anticoagulant”/anti-protein S/anti-cardiolipins, etc.)

An overall pro-coagulative tendency is seen in APS. However, platelets are destroyed by the circulating Abs against their membrane components, and factors are used up in clotting, leading to a ‘consumptive coagulopathy’ similar to that seen in DIC.

Other causes of ↓ production:

liver failure → ↓ TPO

leptospirosis (especially Weil’s disease, the severe form)

numerous hereditary syndromes affecting platelets (ex: “grey platelet syndrome” - lack of α granules)

Other causes of ↑ destruction:

many of the purpuras

hemolytic-uremic syndrome

hypersplenism

Dengue fever / Zika virus

Gaucher’s disease (glucocerebrosidase deficiency)

Medications + other causes:

methotrexate (immunosuppressant); interferon (anti-viral); PPIs

snake bites; Lyme disease; niacin toxicity

** thrombo-CYTHEMIA (higher not lower :) )

APLS is a hyper coagulability disorder so it doesn’t make sense for her to have it if she shows increased bleeding.

this was mentioned as a possible cause in our class, due to a ‘consumptive coagulopathy’ similar to DIC

Question 34

3) The patient is a 28-year-old female who has pronounced bleeding after tooth extraction and menorrhagia, which has caused repeatedly an iron deficiency anemia.Bleedingfromcutsisprolongedandlarge hematomas may appear after bruising.

A brother of the patient and her son are affected by similar bleeding tendency.

Laboratory data:

Platelet count: 176 G/l (normal: 150-400 G/l)

Bleeding time: longer than 30 min (normal: 4-6 min)

Platelet adhesion: abnormal

ADP induced aggregation: normal

Clot retraction: normal

aPTT: 55 sec (normal: 35-45 sec)

Thrombin time: 21 sec (20-22 sec)

What is most likely the diagnosis?

Answer 34

Platelet count is normal (150-400 G/l)

Prolonged bleeding time indicates issues with platelet plug formation / capillary-platelet interaction

Abnormal adhesion, but normal aggregation + retraction indicates issues with vWF or glycoproteins involved in vWF binding (GpIb-IX-V)

Slightly prolonged aPTT indicates issues with the intrinsic pathway of coagulation

• This may indicate specifically vWD rather than BSS, since the intrinsic pathway would be negatively affected by a lack of vWF and its ability to bind and lengthen the serum half-life of factor VIII. GpIb deficiency seen in BSS would probably not cause such issues.

Thrombin time is normal

Occurrence of the same issues in the brother and son indicates a hereditary etiology, but since the patient is female, x-linked recessive disorders such as the hemophilias are unlikely.

Most likely diagnoses are von Willebrand disease or Bernard-Soulier syndrome

von Willebrand Disease (vWD) - deficient quality / quantity of vWF

vWF mainly active in areas of high blood flow / shear stress - deficiency tends to show in skin, GI, uterus

can measure amounts of vWF in blood as well as its capability to bind GpIb / ristocetin

ristocetin - a bacterially-derived antibiotic, can cause platelet agglutination in the presence of vWF; if added to blood deficient of vWF or GpIb, will not cause agglutination

Bernard-Soulier Syndrome (BSS) - AKA hemorrhagiparous thrombocytic dystrophy

an AR coagulopathy caused by GpIb deficiency (vWF-R on platelets)

some signs are perioperative bleeding, nosebleeds, bleeding gums, abnormal menses, abnormal bruising, all of which are seen in this patient

marrow smears / FCT show giant platelets, ↑ megakaryocytes + thrombocytopenia

Differential diagnosis of BSS and vWD is based on a ristocetin test, followed by retesting of the patient’s sample with added healthy plasma.

• Ristocetin will not agglutinate platelets in BSS or vWD due to deficiency of either GpIb or vWF → no agglutination indicates presence of one of these
• Addition of normal, healthy plasma means addition of vWF → if platelets still do not agglutinate, then a GpIb deficiency is indicated → diagnose BSS

Question 35

4) A 41 year old woman has had 3 spontaneous abortions and later gave birth to a premature baby. She was diagnosed to have SLE (systemic lupus erythematous) 5 years ago. She has been admitted to the hospital today with a strong pain in her left leg.

Some of her laboratory results:

WBC: 10 G/l (normal: 4-10 G/l)

ESR: 20 mm/h (normal female: 2-20 mm/h)

D-dimer: strongly positive (>3μg/ml)

aPTT: 62 sec (normal: 35-45 sec)

Thrombin time: 20 sec (normal: 20-22 sec)

What can be the cause of her complains, and how can we prove it?

Answer 35

High-normal WBCs (normal 4-10 G/l)

High-normal ESR (normal < 20 mm/h) indicates mild inflammation

• ESR elevation is often seen in SLE, but is not specific to SLE.

Here it may just be due to inflammatory component of thrombosis.

Positive D-dimers indicate increased thrombolysis

Elevated aPTT (normal 35-45 sec) indicates issues Lupus Anticoagulant effect:

antiphospholipids that in vitro are anti-coagulant by inhibiting the intrinsic pathway, leading to a longer aPTT, yet in vivo they function as pro-coagulants.

Thrombin time is normal, indicating normal cleavage of fibrinogen

Cause of her complaints is probably DVT due to anti-phospholipid syndrome seen commonly in SLE.

Diagnosis can be proven by doppler US of the left thigh and a blood test for auto-antibodies to confirm the APS.

also causes pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia.

Question 36

5) A 3-year-old boy, who suffered from frequent hematomas since he first started to walk, developed a large swelling on his head following a fall. After admission to hospital the surgeon was looking for an abscess, but found blood instead. He is slightly anemic.

Laboratory parameters:

Platelet count: 164 G/l (normal: 150-400 G/l)

Bleeding time: 4 min (normal: 4-6 min)

Prothrombin time: INR = 1,12 (normal: 0,8-1,2)

aPTT: 60 sec (35-45 sec)

Thrombin time: 20 sec (normal: 20-22 sec)

Euglobulin lysis time: 140 min, normal

What tests are necessary to establish diagnosis?

Answer 36

Platelets are normal (150-400 G/l)

Bleeding time is normal (4-6 min.)

INR is normal (0.8-1.2)

Prolonged aPTT (normal: 35-45 sec) indicates potential issue with intrinsic pathway of coagulation (which involves factors VIII8/IX9/XI11, so hemophilia is likely)

Thrombin time is normal (20-22 sec)

Normal euglobulin lysis time (ELT) indicates normal fibrinolysis

ELT is measured by adding citrated platelet-poor plasma to acid to precipitate clotting factors into a “euglobulin fraction”

(fibrinogen, PAI-1, tPA, plasminogen, α-2 antiplasmin and FVIII);

resuspension of euglobulin fraction in borate w/ addition of CaCl2 activates clotting; fibrinolysis is then observed at 10-minute intervals by spectrophotometry

Presence of these symptoms in a boy starting at an early age is indicative of X-linked hereditariness of the disease.

Tests to establish a hemophilia diagnosis include factor assays for factors VIII / IX / XI

Question 37

6) The patient is a 27-year old pregnant woman without a history of bleeding symptoms. She is in her 38th week of pregnancy with her fourth child. Four hours
before admission she suddenly experienced a severe pain in the abdomen followed by start of birth pains that were almost continuous. Half an hour after admission she lost some blood from her vagina that did not clot. The uterus was found totally contracted on physical examination. Fetal heart sounds are not detectable.

Laboratory data:

Platelet count: 20 G/l (normal: 150-400 G/l)

Bleeding time: 8 min (normal: 4-6 min)

Prothrombin time: INR = 4,29 (normal: 0,8-1,2)

aPTT: 80 sec (normal: 35-45 sec)

Thrombin time: 30 sec (normal: 20-22 sec)

What is the probable cause of bleeding? How do you think the FDP concentration changes in this condition?

Answer 37

Low platelets (normal: 150-300 G/l) indicate thrombocytopenia, which can have numerous causes (see Question 2 for list)

Prolonged bleeding time (normal 4-6 min) indicates an issue with platelet plug formation

Prolonged prothrombin time indicates an issue with the extrinsic pathway (TF, etc.)

an INR > 4 is considered to be life-threatening

Prolonged aPTT indicates in issue with the intrinsic pathway (XII, kallikrein, etc.)

Prolonged thrombin time indicates an issue with fibrinogen cleavage

Severe abdominal pain, unclotting vaginal blood loss, a contracted uterus, and absence of fetal heart sounds all point to DIC as a result of spontaneous abortion/miscarriage and the resulting release of fetal clotting factors into the maternal circulation.

This may be “septic abortion”, due to infection, but the question doesn’t give enough info to be sure.

FDP (fibrin degradation product) concentration would increase in this condition, as fibrinolysis increases.

FDP is an older, less specific test for fibrinolysis activity that includes the A and B peptides cleaved off by plasmin. It has mostly been replaced now by tests for D-dimers only.

.

Question 38

7) A 34 year old previously healthy woman suddenly got sick after having arrived to her hotel from a long trip. She had dyspnea and hemoptysis (coughing up blood). She is found to have tachypnea, tachycardia and distended neck veins on physical examination. What is most likely her diagnosis, and what tests can we use to support it? What may be the cause of her problem?

Answer 38

“Tourist class syndrome”

A long air trip (and the resulting prolonged inactivity) is a risk factor for deep vein thrombosis.

Dyspnea, hemoptysis, tachypnea and tachycardia are all signs of pulmonary embolism.

Distended neck (jugular) veins indicate retrograde RHF(Right Heart Failure), which is often a result of pulmonary embolism.

The most likely diagnosis is DVT leading to PE, which can be confirmed with CT pulmonary angiography, chest x-ray, and possibly doppler US on the legs to check for leftover signs of the DVT.

The cause of the problem was most likely the inactivity / immobility and resulting venous stasis during her long air trip.

immobility leads to stasis because of lack of the interaction between the venous valves and perivenous muscle use,

Important to note her age and that she is otherwise healthy, and that people fly all the time and don’t necessarily get DVTs.

possible predisposing factors:

Factor V leiden

Congenital AT III deficiency

Smoking

Oral Contraceptives are known to interfere with almost all haemostatic parameters

• i.e. plasma levels of coagulation factors, anticoagulant proteins and proteins involved in the fibrinolytic pathway change during OC use.

Types (inherited):

Protein C deficiency

Protein S deficiency

Prothrombin gene mutation

Acquired risk factors:

Immobilization →prolonged travel (airplane) →muscular pump is not used→ stasis increased risk for thrombus

Estrogens →maybe she is on contraceptives

Tests:

Chest X-ray (look for embolism)

ECG (S1Q3 syndrome)

Doppler (also exclude MI)

Check hypercoagulability → she is quite young, so screen for underlying hypercoagulability.

Question 39

8) A 53 year old woman has a bleeding tendency since she was a child. She got a bump on her forehead two days ago, and now has a dark, purple periorbital hematoma

Laboratory findings:

Platelet count: 250 G/l (normal: 150-400)

Bleeding time: longer than 30 min (normal: 4-6 min)

Prothrombin time: INR = 1,16 (normal: 0,8-1,2)

aPTT: 30 sec (normal: 35-45 sec)

Thrombin time: 20 sec (normal: 20-22 sec)

Platelet adhesion and aggregation: decreased

Clot retraction: less than normal

What may cause her bleeding tendency?

Answer 39

Platelet count is normal (150-400 G/l)

Prolonged bleeding time (normal: 4-6 min)

Normal INR (0.8-1.2)

Normal aPTT (35-45 sec … actually short but not an issue, I think)

Normal thrombin time (20-22 sec)

Decreased platelet adhesion/aggregation indicate possible issues with vWF, GpIb etc.

To test adhesion and aggregation, various agents (epinephrine, ristocetin, ADP, collagen, snake venom, thrombin) can be used in vitro as a platelet activator; progress is monitored via turbidimetry (“turbidimetric aggregometry”)

Decreased clot retraction indicates possible Glanzmann’s thrombasthenia

Clot retraction tests indicate:

1) number/quality of platelets
2) fibrin concentration
3) fibrinolytic activity
4) packed cell volume (AKA hematocrit)

Lower hematocrit means stronger clot retraction

Retraction depends on factors released by platelets caught in the fibrin mesh of the clot → ↓ retraction may mean some form of thrombocytopenia or thrombasthenia

Since her platelet count is normal, this is not a thrombocytopenia. Some problem with the quality of the platelets must exist. This could be one of several things:

Glanzmann’s Thrombasthenia - deficiency of Gp2b/3a the platelet membrane
receptor for fibrinogen

Bernard-Soulier Syndrome - GpIb deficiency, discussed earlier (question 3)

von Willebrand Disease - defect in vWF amount or function, 4 types:

Type 1 - 60-80% of cases; heterozygous gene defect; ↓ vWF amount

Type 2 - 20-30% of cases; qualitative defect

Type 3 - most severe; homozygous gene defect; complete vWF absence

Platelet-Type - GpIb issue; may be same as Bernard-Soulier?

I think it is this one due to the decreased clot retraction (which you need GpIIb/IIIa for)

Question 40

9) A 76 year old male has been on anticoagulant therapy for years because of his chronic atrial fibrillation. He has been recently treated with a broad spectrum antibiotic for his febrile illness. He has been complaining of frequent nosebleeds since yesterday. His stools have turned tar-like. What can be the cause of his complains and what is to be done?

Answer 40

Black, tarry stools (known as “melena”) are a sign of upper GI tract bleeding; the blood darkens as its hemoglobin is altered by digestive enzymes and bacterial flora.

Warfarin is commonly prescribed as an anticoagulant for patients with atrial fibrillation to avoid thrombus formation, which increases (especially in the auricle) due to atrial stasis.

Cause:

Many antibiotics interact with warfarin to cause an increased bleeding tendency:

These antibiotics include: trimethoprim/sulfamethoxazole (TMP/SMX), metronidazole, fluconazole, ciprofloxacin, levofloxacin, azithromycin, and clarithromycin

(Put more simply, some -azoles, fluoroquinolones and macrolides)

This occurs via two mechanisms:

Inhibition of hepatic CYP450 enzymes involved in warfarin metabolism

Clearance of vitamin K-synthesizing intestinal flora; resulting decrease in circulating vitamin K negatively affects clotting ability via decreased gamma-carboxylation of clotting factors II, VII, IX and X

Treatment:

Vitamin K administration to replace the missing vitamin K

Heparin may be administered to provide anticoagulant effects while the vitamin K levels are being worked out.

Either temporary suspension/reduction of warfarin treatment until the antibiotic course is complete, or switching antibiotics could be an effective way to stop the bleeding.

Question 41

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 41

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 42

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 42

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 43

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 43

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 44

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 44

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 45

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 45

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 46

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 46

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