Myocardial infarction (MI)—heart attack

A. Ischemia versus MI: Ischemia is a reversible mismatch between the supply and demand of oxygen. Infarction
is an irreversible mismatch that results in cell death caused by the lack of blood flow (oxygenation). For instance, chest pain caused by ischemia can be relieved by administering nitroglycerin (a vasodilator) to the patient. If the patient has an MI, the pain will not be relieved with nitroglycerin.

1. MIs most commonly occur when a coronary artery is occluded by a thrombus generated in an atherosclerotic artery.

2. Symptoms include:
a. Chest pain, shortness of breath.
b. Diaphoresis (sweating), clammy hands.
c. Nausea, vomiting.

3. Consequences:
a. Death (one third of patients).
b. Arrhythmias (most common immediate cause of death).
c. Congestive heart failure.
d. Myocardial rupture, which may result in death from cardiac tamponade.
e. Thrombus formation on infarcted tissue; may result in systemic embolism.
 

Urinary tract infection
Most often caused by gram-negative, rod-shaped bacteria that are normal residents of the enteric tract, especially Escherichia coli.

Clinical manifestations: 

frequent urination, dysuria, pyuria (increased PMNs), hematuria, and bacteriuria.

May lead to infection of the urinary bladder (cystitis) or kidney (pyelonephritis).

Pulmonary Hypertension 

Sustained elevation of mean pulmonary arterial pressure.

Pathogenesis 
Elevated pressure, through endothelial cell dysfunction, produces structural changes in the pulmonary vasculature. These changes ultimately decrease pulmonary blood flow and stress the heart to the point of failure. Based on etiology, pulmonary hypertension is divided into two categories.

Primary (idiopathic): The cause is unknown.
Secondary: The hypertension is secondary to a variety of conditions which increase pulmonary blood flow or increase resistance to blood flow. Example: Interstitial fibrosis.
Pathology 
The changes involve large and small pulmonary blood vessels and range from mild to severe. The major changes include atherosclerosis, striking medial hypertrophy and intimal fibrosis of small arteries and arterioles, and plexogenic arteriopathy. Refer to Figure 15-7 in your textbook.

Pathophysiology 
Dyspnea and fatigue eventually give way to irreversible respiratory insufficiency, cyanosis and cor pulmonale.

Hyperparathyroidism

Hyperparathyroidism is defined as an elevated secretion of PTH, of which there are three main types:
1. Primary—hypersecretion of PTH by adenoma or hyperplasia of the gland.
2. Secondary—physiological increase in PTH secretions in response to hypocalcaemia of any cause.
3. Tertiary—supervention of an autonomous hypersecreting adenoma in long-standing secondary hyperparathyroidism.

Primary hyperparathyroidism
This is the most common of the parathyroid disorders, with a prevalence of about 1 per 800 
It is an important cause of hypercalcaemia.
More than 90% of patients are over 50 years of age and the condition affects females more than males by nearly 3 : 1.

Aetiology

Adenoma 75%  -> Orange−brown, well-encapsulated tumour of various size but seldom > 1 cm diameter Tumours are usually solitary, affecting only one of the parathyroids, the others often showing atrophy; they are deep seated and rarely palpable.

Primary hyperplasia 20%  ->  Diffuse enlargement of all the parathyroid glands

Parathyroid carcinoma 5% -> Usually resembles adenoma but is poorly encapsulated and invasive locally.

Effects of hyperparathyroidism
The clinical effects are the result of hypercalcaemia and bone resorption.
 

Effects of hypercalcaemia:
- Renal stones due to hypercalcuria.
- Excessive calcification of blood vessels.
- Corneal calcification.
- General muscle weakness and tiredness.
- Exacerbation of hypertension and potential shortening of the QT interval.
- Thirst and polyuria (may be dehydrated due to impaired concentrating ability of kidney).
- Anorexia and constipation    

Effects of bone resorption:
- Osteitis fibrosa—increased bone resorption with fibrous replacement in the lacunae.
- ‘Brown tumours’—haemorrhagic and cystic tumour-like areas in the bone, containing large masses of giant osteoclastic cells.
- Osteitis fibrosa cystica (von Recklinghausen disease of bone)—multiple brown tumours combined with osteitis fibrosa.
- Changes may present clinically as bone pain, fracture or deformity.

 about 50% of patients with biochemical evidence of primary hyperparathyroidism are asymptomatic.

Investigations are:
- Biochemical—increased PTH and Ca²⁺ , and decreased PO₄^3- .
- Radiological—90% normal; 10% show evidence of bone resorption, particularly phalangeal erosions.

Management is by rehydration, medical reduction in plasma calcium using bisphosphonates and eventual surgical removal of abnormal parathyroid glands.

Secondary hyperparathyroidism 

This is compensatory hyperplasia of the parathyroid glands, occurring in response to diseases of chronic low serum calcium or increased serum phosphate.
Its causes are:
- Chronic renal failure and some renal tubular disorders (most common cause).
- Steatorrhoea and other malabsorption syndromes.
- Osteomalacia and rickets. 
- Pregnancy and lactation.

Morphological changes of the parathyroid glands are:
- Hyperplastic enlargement of all parathyroid glands, but to a lesser degree than in primary hyperplasia.
- Increase in ‘water clear’ cells and chief cells of the parathyroid glands, with loss of stromal fat cells. 

Clinical manifestations—symptoms of bone resorption are dominant.

Renal osteodystrophy
Skeletal abnormalities, arising as a result of raised PTH secondary to chronic renal disease, are known as renal osteodystrophy.

Pathogenesis

renal Disease + ↓  vit. D activation , ↓ Ca 2+  reabsorption  → ↓  serum Ca 2+ → ↑ PTH → ↓ bone absorption

Abnormalities vary widely according to the nature of the renal lesion, its duration and the age of the patient, but include:
- Osteitis fibrosa .
- Rickets or osteomalacia due to reduced activation of vitamin D.
- Osteosclerosis—increased radiodensity of certain bones, particularly the parts of vertebrae adjacent to the intervertebral discs.

The investigations are both biochemical (raised PTH and normal or lowered Ca 2+ ) and radiological (bone changes).
Management is by treatment of the underlying disease and oral calcium supplements to correct hypocalcaemia.

Tertiary hyperparathyroidism
This condition, resulting from chronic overstimulation of the parathyroid glands in renal failure, causes one or more of the glands to become an autonomous hypersecreting adenoma with resultant hypercalcaemia. 

Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema 
 >80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes 
 
 Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension 

Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
    o Minimal change disease (MCD)
    o Focal segmental glomerulosclerosis
    o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
    o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
    o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
    o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma  
    
 - Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.  

Investigations

- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.

Management

- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin. 

Nephritic Syndrome 

Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red 

Causes

1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis

Clinical Features

- Abrupt onset of :
    o Glomerular haematuria (RBC casts or dysmorphic RBC)
    o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
    o Oedema (periorbital, sacral )
    o Hypertension
    o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.

Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders 

Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria. 

Fungal
 
Superficial mycoses

1. Superficial mycoses→outermost layers of the skin or its appendages; skin, nails and/or hair.
2. Dermatophytoses transmitted by contact with man (anthropophilic; weak inflammatory response), animals (zoophilic; brisk inflammatory response), or contact with soil (geophilic; strongest inflammatory response).
3. Trichophyton→hair, skin, or nails; Microsporum → hair and skin; and Epidermophyton→skin alone.
4. The diagnosis is best made by culture of skin scrapings secured from the leading edge of the lesion.
 - use Wood's light to check for fluorescing metabolites.
 - direct KOH preparations of the scraped material
 
 Subcutaneous Mycoses
 
1. Subcutaneous mycoses are usually related to traumatic implantation into the skin.
2. Chromoblastomycosis, or verrucous (wart-like) dermatitis, is a chronic skin lesion associated with several pigmented fungi (Fonsecaea, Phialophora, and Cladosporium).
 - granulomatous reaction in subcutaneous tissue are pigmented, thick walled bodies are visible in tissue section.
3. Mycetomas (maduromycosis) are characterized by a localized, tumorous nodule (usually foot) that occurs in response to chronic progressive destruction of skin, subcutaneous tissue, fascia, muscle and bone 

4. Sporotrichosis is caused by the dimorphous fungus, Sporothrix schenckii.
 - traumatic implantation of the fungus growing in soil, thus the association with "rose gardeners disease".
 - MC lymphocutaneous disease → painless nodule at inoculation site → chain of suppurating subcutaneous nodules that drain to the skin surface along the course of the lymphatics.

- cigar shaped yeast forms are seen in the suppurative nodules and asteroid bodies (Splendore-Hoeppi phenomenon) are noted within granulomatous microabscesses.
 - treatment: oral potassium iodide