godfather of surgery

Chapter 1284 The Last Bread

After Ms. Lin left, Li Min finished tidying up his notes and couldn't help but ask, "Professor Yang, if it really is chronic exposure to heavy metals, why didn't so many hospitals, including some top hospitals, detect it before? Routine heavy metal screening should include lead, mercury, and arsenic, and cadmium is sometimes tested, but cobalt is indeed uncommon."

Yang Ping withdrew his gaze and looked at the eager-to-learn Dr. Li: "Good question. First, routine screening targets clear occupational exposures or typical poisoning symptoms. Ms. Lin is an architectural designer who enjoys gardening and painting, which are not considered high-risk professions in conventional understanding. Second, her symptoms lack specificity and are scattered across multiple systems—bones, nerves, skin, etc.—making them easily analyzed by various specialists without a holistic perspective connecting them. Third, and most importantly," he paused, "chronic low-level exposure to toxins may result in blood drug concentrations that are entirely within the normal reference range, or even fluctuate intermittently. Toxicology focuses on the body's load and biological effects, not just instantaneous blood concentrations. Cobalt and cadmium are both osteophilic elements that deposit in bones and are slowly released, interfering with local bone metabolism over the long term. Urine excretion tests, especially 24-hour urine or stimulated urine excretion, sometimes reflect the body's load better than blood values."

Li Min suddenly realized: "So, you had her test for cobalt and cadmium in her 24-hour urine to see the total excretion and assess the level of accumulation in her body?"

“That’s right. At the same time, we also need to see if these elements have already caused functional consequences. For example, cadmium damages the kidneys, and in the early stages, it may manifest as abnormal renal tubular function, such as low molecular weight proteinuria and elevated urinary β2-microglobulin, which are easily overlooked in routine urinalysis. Cobalt interferes with mitochondrial and vitamin B12 metabolism, which may lead to megaloblastic anemia or elevated homocysteine ​​levels. However, her blood routine was basically normal, so the damage may not have reached the point of affecting hematopoiesis yet, but it is enough to cause insufficient power supply to bone cells and nerve cells with vigorous energy metabolism.” Yang Ping explained, while silently perfecting the chain of reasoning in his mind. “The skeleton is a highly active organ that is constantly remodeling. The balance between osteoblasts and osteoclasts is extremely delicate. Any factor that affects the energy or mineral supply to cells may lead to an imbalance in remodeling, making local microstructures fragile, thereby causing pain.”

After thinking for a while, Li Min felt he had grasped Professor Yang's train of thought and said, "Professor Yang, I have contacted the laboratory and endocrinology departments. Ms. Lin's special tests have been expedited, and we can have her blood and urine drawn as early as tomorrow. I have also contacted the occupational disease department and the pathology department, and they have indicated that they will fully cooperate. As for the bone biopsy, we need to wait for the blood test results to provide preliminary indications before making an assessment. I have already set aside a time window."

"Very good." Yang Ping nodded. "Set Ms. Lin's case as a priority case, and notify me immediately of any results."

At this moment, several graduate students tiptoed in, and Li Min said to them, "Is your graduate student meeting over?"

One graduate student replied, "It's over."

“While you were away, we encountered another difficult case. It’s such a pity,” Li Min said, shaking his head.

The graduate students immediately crowded around to see Li Min's notes, wondering how he could have missed so much while attending a meeting: "What cases? Let me see."

……

Over the next two days, Yang Ping remained busy with outpatient clinics, surgeries, and consultations. The spinal surgery plan for the Middle Eastern royal family member, after several revisions, was finally finalized. The surgery date was set for one month from now, at which time he would arrive at the Sanbo Research Institute in advance.

On the afternoon of the third day, Li Min practically ran into Yang Ping's office with a stack of newly completed reports in his hand.

"Professor Yang, the results are in!" Li Min's voice was filled with suppressed excitement.

Yang Ping took the report and quickly skimmed through it.

Blood tests: Cobalt: 3.2 nmol/L (reference range: < 2.0 nmol/L), slightly elevated. Cadmium: 1.8 μg/L (reference range: < 1.0 μg/L), slightly elevated. Lead, mercury, and arsenic levels were all within the normal range. Calcium and phosphorus levels were normal. Magnesium: 0.70 mmol/L (reference range: 0.75-1.05 mmol/L), at the lower limit of normal. Alkaline phosphatase (ALP): 135 U/L (slightly elevated; previous tests showed fluctuations within the upper limit of normal). Parathyroid hormone (PTH): 68 pg/mL (slightly high). 25-hydroxyvitamin D: 18 ng/mL (insufficient). 1,25-dihydroxyvitamin D: low. Fibroblast growth factor 23 (FGF23): normal.

Bone turnover markers: Type I procollagen N-terminal propeptide (P1NP): 85 μg/L (significantly elevated, indicating active bone formation); β-collagen specific sequence (β-CTX): 1.2 ng/mL (significantly elevated, indicating active bone resorption). Both were several times higher than normal, indicating a high bone turnover status.

Other findings: Serum copper and zinc levels were normal. Renal function tests showed normal creatinine, but urinary β2-microglobulin was 450 μg/L (significantly elevated, suggesting renal tubular damage). Homocysteine ​​was slightly elevated. Complete blood count showed no significant abnormalities.

24-hour urine test: urinary cobalt excretion: 45 μg/24h (significantly higher than normal).

Urinary cadmium excretion: 18 μg/24h (significantly higher than normal).

Increased urinary calcium and phosphorus excretion.

Yang Ping's gaze lingered on several key data points for a long time. Mildly elevated blood cobalt and cadmium levels, combined with a significant increase in urinary excretion, strongly suggested an excess of cobalt and cadmium in the body, which was actively trying to eliminate them. Low blood magnesium, insufficient vitamin D, and compensatory increases in PTH indicated a mild disorder of calcium and magnesium metabolism. However, the most indicative indicators were a high bone turnover state and renal tubular damage.

"As expected..." Yang Ping muttered to himself. His reasoning had been initially verified.

The combined effects of cobalt and cadmium may have disrupted Ms. Lin's bone health through multiple pathways: direct osteocyte toxicity, interference with mineral metabolism, particularly affecting calcium, phosphorus, and magnesium reabsorption through kidney damage, and potential oxidative stress and mitochondrial dysfunction. High bone turnover means the bones are "busy" constantly patching up existing bone, but the newly formed bone matrix may be of poor quality, with poor mineralization or abnormal collagen cross-linking, leading to decreased bone strength and microscopic damage and pain at stress concentration sites. Renal tubular damage is a typical early manifestation of cadmium toxicity.

"This explains why her inflammatory markers aren't high, because it's not a typical inflammatory disease at all," Li Min said excitedly. "It's a bone metabolism disorder caused by toxin metabolism. Professor Yang, can we diagnose 'chronic cobalt and cadmium poisoning-related bone disease'?"

“We’re still one step away,” Yang Ping said calmly. “These indicators suggest poisoning and metabolic disorders, and they also explain the increased bone turnover and kidney damage, but we need more direct evidence to prove that her bone microstructure has indeed been damaged as a result, and to rule out other diseases that could lead to high bone turnover. Histomorphometry from a bone biopsy can give us the answer, to see if her trabeculae are thinned or broken, if there is an abnormal increase in bone turnover units, and if bone matrix mineralization is delayed or poor.”

Li Min picked up the phone and dialed Ms. Lin's number directly. The call was quickly answered, and Ms. Lin's nervous yet expectant voice came through: "Dr. Li?"

“Ms. Lin, the test results are in, and there are some important findings,” Li Min said in a calm and clear tone. “The levels of cobalt and cadmium in your blood and urine are indeed outside the normal range, indicating chronic excessive exposure. At the same time, your bone metabolism is abnormally active, and your kidneys have shown early signs of damage. These findings are biologically related to your long-term exposure to pigments containing cobalt and cadmium.”

There was a few seconds of silence on the other end of the phone, followed by a sigh of relief: "Five years... finally... finally something makes sense..." It wasn't sadness, but a near-exhausting sense of confirmation. "However," Li Min continued, "to definitively confirm the diagnosis and guide precise treatment, we need to perform an invasive procedure—an iliac bone biopsy. This is the most direct way to obtain the microscopic structure of your bones, telling us exactly what happened to them. The procedure requires local anesthesia, there will be a small incision and slight pain, but the risks are manageable. You need to consider this carefully."

"I'll do it!" Ms. Lin answered without hesitation. "As long as it can be figured out and cured, I'm willing to do anything. I've had enough of speculation and ineffective treatments over the past five years. Please make the arrangements."

"Okay. Come over when you have time, and I'll discuss the pre-operative preparations and risks with you in detail and make arrangements as soon as possible." Li Min hung up the phone.

The bone biopsy was scheduled for two days later. Li Min performed the procedure, surrounded by many graduate students.

To ensure accurate sampling, under CT guidance, Li Min used a special puncture needle to extract a cylindrical bone tissue specimen, about the thickness of a pencil lead and a little over one centimeter long, from Ms. Lin's posterior superior iliac spine. The procedure went very smoothly, and Ms. Lin experienced only soreness at the puncture site, with little discomfort.

The specimens were quickly sent to the pathology department for non-decalcified bone sectioning. This is a special technique that preserves the original mineral composition of the bone for bone histomorphometric analysis—precisely measuring the thickness, number, and separation of trabeculae under a microscope, calculating the bone volume fraction, observing osteoblast and osteoclast activity, and assessing the degree of bone matrix mineralization.

It will take several days to get the results.

Over the past few days, Yang Ping had Li Min systematically review literature on the toxicity of cobalt and cadmium, particularly their effects on bones and kidneys. They found that while cases of acute poisoning had been reported, cases like Ms. Lin's, where prolonged exposure to low-level art materials led to such subtle and complex symptoms, were extremely rare, with very little literature documenting them. This further highlighted the importance of a definitive diagnosis.

Meanwhile, based on the existing results, Yang Ping began to conceive a preliminary intervention plan. If the bone biopsy confirms that the damage to the bone microstructure is related to heavy metal load, then the core of the treatment will be: to completely avoid further exposure: replace all painting materials containing cobalt and cadmium, strictly implement protective measures, and even consider suspending the hobby of painting for a period of time.

He dictated the treatment, Li Min recorded it, and the graduate students next to him all opened their notebooks and began to rustle as they took notes.

Promoting heavy metal excretion: For chronic, low-level poisoning, the need for chelating agents such as EDTA and DMSA requires an assessment of benefits and risks, as they may increase the burden on the kidneys or lead to the loss of other elements. However, nutritional support for detoxification can be tried: supplementing with zinc and selenium to counteract cadmium toxicity, antioxidants such as N-acetylcysteine, vitamins C and E, and sufficient magnesium and B vitamins to support metabolism and nerve function.

Correcting metabolic disorders: Supplementing with vitamin D to reach adequate levels, optimizing calcium and magnesium intake, and ensuring high-quality protein, which is the building block of bone matrix.

Bone support and pain management: In a state of high bone turnover, the use of anti-bone resorption drugs, such as bisphosphonates, should be approached with extreme caution and must be based on bone biopsy results, as such drugs may interfere with the bone's own repair process.

Pain management may require the use of medications that regulate nerve sensitization, but care must be taken to avoid exacerbating fatigue.

"You've written it all down?" Only after saying that did Yang Ping realize that he might have spoken too quickly.

Li Min closed his textbook: "I've written it all down." He had developed shorthand skills during his studies.

A week later, the pathology report from the bone biopsy finally came out.

Li Min took the thick report and immediately went to find Yang Ping. Yang Ping took it and carefully read the pathological description and the series of precise measurement data: Bone volume fraction (BV/TV): slightly decreased. Trabecular thickness (Tb.Th): thinned. Trabecular separation (Tb.Sp): increased. Osteoblast surface (Ob.S/BS) and osteoclast surface (Oc.S/BS): both significantly increased, confirming a high bone turnover state. Mineralization deposition rate (MAR): low to normal. Bone formation rate (BFR/BS): increased. Localized osteoid tissue (unmineralized bone matrix) was observed to be slightly widened, with irregular mineralization fronts.

The pathological diagnosis concluded that the patient exhibited changes consistent with high-turnover metabolic bone disease, accompanied by mildly delayed mineralization. These findings require clinical correlation and should be considered in relation to bone metabolic disorders caused by chronic heavy metal exposure (cobalt/cadmium).

"The evidence is irrefutable." Yang Ping breathed a sigh of relief and handed the report to Li Min.

"The pathological examination results once again confirmed our suspicions. Her bones were indeed 'busying themselves,' with an imbalance between demolition and reconstruction, deteriorating structure, declining quality, and affecting mineralization. Those migratory bone pains were warning signals from these vulnerable areas during normal activity."

Yang Ping personally explained the final diagnosis and treatment plan to Ms. Lin. As Ms. Lin listened to the unfamiliar toxicology and bone metabolism terms, a sense of relief she hadn't felt in five years shone in her eyes. It wasn't fear of the disease, but rather a sense of relief that the "enemy" had finally revealed itself.

“Professor Yang, thank you… thank you so much for finding it.” Ms. Lin’s voice choked with emotion. “We finally figured out what happened.”

“Your understanding and cooperation are crucial,” Yang Ping said gently. “Next, we will focus on the treatment. This is completely curable, so there’s no need to worry too much.”

"If I had known, I would have come directly here. I wouldn't have had to go through five years of this and become depressed," Ms. Lin said emotionally.

Li Min immediately comforted her: "That's not a waste of time. Just because we made you full with the last piece of bread doesn't mean you should deny the bread you ate before."

Ms. Lin felt that Dr. Li's analogy was unreasonable: "But if it weren't for your bread, I might never have enough to eat in my life."