Assignment details

25.1. HLTH502: Applied Pathophysiology

Max is a 57-year-old man with a history of liver cirrhosis due to a chronic hepatitis C virus (HCV) infection that was diagnosed in his mid-thirties. Max was treated for an upper gastrointestinal haemorrhage due to oesophageal varices two years ago and is currently prescribed diuretics to treat ascites.

Max was seen at the Gastrointestinal Outpatient Clinic one week ago.

The current laboratory test results showed a decline in his renal function.

Case Study: John – A 75-Year-Old Man with Multiple Diabetic Complications

Patient Presentation

John is a 75-year-old man living alone with a history of type 2 diabetes (diagnosed at age 52) managed with insulin. He has developed diabetic kidney disease and diabetic neuropathy with diabetic foot disease. His recent presentation includes:

• Weight: 89.3 kg, Height: 172 cm (BMI: 30.2 – obese)
• Elevated blood pressure: 148/94 mmHg
• Complaints of unsteadiness, dizziness when walking
• Foot pain, numbness, and tingling affecting balance
• Foot examination reveals dry skin, calluses, non-healing ulcer on right foot
• Reduced sensation, poor circulation (delayed capillary refill, mild swelling)

Recent Laboratory Results

Pathophysiological Mechanisms

Chronic Hyperglycemia and Cellular Changes

John’s persistently elevated blood glucose (evidenced by HbA1c of 88 mmol/mol) drives multiple pathogenic pathways:

1. Advanced Glycation End-products (AGEs) Formation

Chronic hyperglycemia leads to non-enzymatic glycation of proteins and lipids, forming AGEs that:

• Cross-link with collagen in blood vessels, reducing elasticity
• Bind to RAGE receptors, activating pro-inflammatory pathways
• Contribute to basement membrane thickening in renal glomeruli

2. Polyol Pathway Activation

Excess glucose is shunted into the polyol pathway where:

• Glucose is converted to sorbitol by aldose reductase
• Sorbitol accumulation in Schwann cells contributes to neuropathy
• NADPH depletion reduces glutathione regeneration, increasing oxidative stress

Diabetic Kidney Disease

John’s eGFR of 32 ml/min/1.73m² and ACR of 36.4 mg/mmol reflect advanced diabetic nephropathy:

Glomerular Changes

• Mesangial expansion due to ECM accumulation
• Podocyte injury and loss leading to proteinuria
• Glomerular basement membrane thickening

Tubulointerstitial Changes

• Interstitial fibrosis and tubular atrophy
• Inflammatory cell infiltration
• Peritubular capillary rarefaction

Diabetic Neuropathy and Foot Complications

John’s symptoms of pain, numbness, tingling, and unsteadiness reflect mixed sensorimotor and autonomic neuropathy:

Nerve Fiber Damage

• Axonal degeneration and demyelination
• Reduced nerve conduction velocity
• Small fiber neuropathy contributing to pain symptoms

Microvascular Changes

• Endoneurial capillary basement membrane thickening
• Reduced blood flow leading to nerve ischemia
• Impaired vasoreactivity

Foot Ulcer Pathogenesis

The non-healing ulcer results from the “triopathy” of:

1. Neuropathy (loss of protective sensation)
2. Angiopathy (impaired circulation)
3. Immunopathy (reduced leukocyte function)

Systemic Effects and Organ Dysfunction

Conclusion

John is a 75-year-old man who lives at home alone. He has a history of type 2 diabetes (diagnosed at 52 years-of-age) and uses insulin preparations for blood glucose control. John has been diagnosed with diabetic kidney disease and diabetic neuropathy with diabetic foot disease.

John attends the diabetic clinical regularly. For the past four months he has been visiting his primary care practice and today he is weighed at 89.3 kg; his height is 172 cm. His blood pressure is slightly increased (148/94). He also mentions feeling “unsteady and a bit dizzy” when walking. He also suffers from pain and notices numbness, and tingling in his feet, making it difficult for him to maintain balance. During his foot examination, John has dry skin, calluses, and a non-healing ulcer on his right foot. During physical examination, the sensory testing shows reduced sensation, and there are signs of poor circulation, (delayed capillary refill and mild swelling). John is suspected of having diabetic foot complications, possibly peripheral arterial disease, and an infected foot ulcer.

Blood tests taken at John’s previous visit one month ago were: HbA1c of 88 mmol/mol, eGFR 32 ml/min/1.73m², albumin: creatinine ratio (ACR) 36.4 mg/mmol and CRP 80 mg/L. Discuss this case describing the mechanisms for acute and chronic cellular and pathophysiological changes responsible for the signs and symptoms displayed by John. Include in your answer associated effects of type 2 diabetes on organ function or dysfunction, and how these link to John’s presentation and symptoms.

Word Count: 2500 words excluding references, up to two figures or tables with no more than 100 words each.

David is a 67-year-old man who has been a smoker since his teens. He commenced vaping eight years ago when he was diagnosed with chronic obstructive pulmonary disease (FEV1 57% predicted volume) and prescribed a triple therapy combination inhaler. He had been coughing up phlegm for a few days, attempted to see his general practitioner but was unable to walk. His wife called an ambulance that brought him to the emergency department.

On admission he was very short of breath, speaking only in short sentences with productive cough and coloured sputum. A chest X-ray and blood samples were taken, and David was transferred to a medical ward with a diagnosis of pneumonia and commenced intravenous antibiotic and fluid infusion. The chest X-ray showed “signs of hyperinflation, with bilateral streaky opacification, greater than on the right than left”. His blood results were: white blood cells 14.8 x 109/L (normal range 4.0-11), neutrophils 9.8 x 109/L (1.9-7.5), arterial blood pH 7.24 (7.35-7.45), P₂CO2 78 mmHg (35-45), PaO2 50 mmHg (75-105), HCO3 29 mmol/L (22-28). His vital signs: respiratory rate 32 bpm, SpO2 92% (6 L-min O2), heart rate 108 bpm, blood pressure 102/64 mmHg, and tympanic membrane temperature 39.7°C.

Discuss this case describing the mechanisms for chronic and acute cellular and pathophysiological changes responsible leading to and causing the signs and symptoms displayed by David. Include in your answer the mechanisms of tobacco addiction, the mechanisms responsible for chronic obstructive pulmonary disease, and the mechanisms and effects of pneumonia on respiratory and cardiovascular function.
Word Count: 2500 words excluding references, up to two figures Ngaitoa is a 12-year-old boy who lives with his parents and four siblings. He attends school and has a good group of friends that he socialises with.

Today he has a sore throat, and as this is the second time in as many weeks that he has a sore throat, he is taken to the local Primary Health Care service. A throat swab is taken by the practice nurse. While at the medical centre the practice nurse asks Ngaitoa if he has had pain or aches in his joints. He tells her he has had some joint ‘aches’, when asked he explains he also has some non-descript chest pain or “tightness” and this sometimes keeps him awake at night. The practice nurse suspects Ngaitoa has rheumatic fever which is later confirmed when the throat swab results indicate a Group A Streptococcus (GAS) infection.
Ngaitoa is scheduled for an echocardiograph that later shows valve regurgitation.

Discuss this case describing in detail 1) the mechanisms for the acute cellular and pathophysiological changes responsible for the signs and symptoms displayed by Ngaitoa. Include in your answer the acute effects of rheumatic fever on cellular and organ function or dysfunction, and how these link to Ngaitoa’s presenting symptoms. Then discuss events in the acute setting responsible for 2) the potential chronic cardiac effects and then 3) the pulmonary effects, including the pathophysiological
mechanisms, and the long-term consequences of 1), 2) and 3).
Word Count: 2500 words excluding references, up to two figures or tables with no more than 100 words each.