Group A Streptococcus
 - scarlet fever usually begins as a Streptococcal pharyngitis/tonsillitis and then develops an erythematous rash beginning on the trunk and limbs with eventual desquamation.
 - rash is due to elaboration of erythrogenic toxin by the organism
 - face is usually spared, but, if involved there is a characteristic circumoral pallor and the tongue becomes bright red, thus the term "strawberry tongue".
 - post-streptococcal immune complex glomerulonephritis is a possible sequela of scarlet fever.
 - Dick test is a skin test that evaluates immunity against scarlet fever; no response indicates immunity (anti-toxin antibodies present); erythema indicates no immunity.
 - impetigo due to Streptococcus pyogenes is characterized by honey colored, crusted lesions, while those with a predominantly bullous pattern are primarily due to Staphylococcus aureus.
 - cellulitis with lymphangitis ("red streaks") is characteristic of Streptococcus pyogenes.
 - hyaluronidase is a spreading factor that favors the spread of infection throughout the subcutaneous tissue unlike Staphylococcus aureus which generates coagulase to keep the pus confined.
 - erysipelas refers to a raised, erythematous ("brawny edema"), hot cellulitis, usually on the face that commonly produces septicemia, if left untreated. 

ESOPHAGUS Pathology

Congenital malformations 
1. A tracheoesophageal fistula (the most prevalent esophageal anomaly) occurs most commonly as an upper esophageal blind pouch with a fistula between the lower segment of the esophagus and the trachea. It is associated with hydramnios, congenital heart disease, and other gastrointestinal malformation. 

2. Esophageal atresia is associated with VATER syndrome (vertebra1 defects, anal atresia, tracheoesophageal fistula, and renal dysplasia)

3. Stenosis refers to a narrowed esophagus with a small lumen.  lt may be congenital or acquired, e.g., through trauma or inflammation. 

Inflammatory disorders 

Esophagitis 

most often involves the lower half of the esophagus.  Caused by the reflux of gastric contents (juices) into the lower esophagus. One of the most common GI disorders.

Clinical features. 

Patients experience substernal burning  associated with regurgitation, mild anemia, dysphagia,  hematemesis, and melena. Esophagitis may predispose to esophageal cancer. 

Etiology

- Reflux esophagitis is due to an incompetent lower esophageal sphincter that permits reflux of gastric juice into the lower esophagus. 
- Irritants such as citric acid, hot liquids, alcohol, smoking, corrosive chemicals, and certain drugs, such as tetracycline, may provoke inflammation. 
- Infectious etiologies include herpes, CMV, and C. albicans. The immunocompromised host is particularly susceptible to infectious esophagitis. 
Although chronic or severe reflux disease is uncommon, consequences of these conditions can lead to Barrett’s esophagus, development of a stricture, or hemorrhage.

Pathology

-Grossly, there is hyperemia, edema, inflammation, and superficial necrosis. 

Complications include ulceration, bleeding, stenosis, and squamous carcinoma. 

Treatment: diet control, antacids, and medications that decrease the production of gastric acid (e.g., H blockers).

Barrett's esophagus, 

gastric or intestinal columnar epithelium replaces normal squamous epithelium in response to  chronic reflux.- A complication of chronic gastroesophageal reflux disease.
- Histologic findings include the replacement of squamous epithelium with metaplastic columnar epithelium.
- Complications include increased incidence of esophageal adenocarcinoma, stricture formation, or hemorrhage (ulceration).

 Motor disorders. 

Normal motor function requires effective peristalsis and relaxation of the lower esophageal sphincter. 

Achalasia is a lack of relaxation of the lower esophageal sphincter (LES), which may be associated with aperistalsis of the esophagus and increased basal tone of the LES. 

Clinical features. Achalasia occurs most commonly between the ages of 30 and 50. Typical symptoms are dysphagia, regurgitation, aspiration, and chest pain. The lack of motility promotes stagnation and predisposes to carcinoma. 

Hiatal hernia is the herniation of the abdominal esophagus, the stomach, or both, through the esophageal hiatus in the  diaphragm.

Scleroderma is a collagen vascular disease, seen primarily in women, that causes subcutaneous fibrosis and widespread  degenerative changes. (A mild variant is known as CREST syndrome which stands for calcinosis. raynaud's phenomenon , esophageal dysfunction, sclerodactyly and telengectseia. esophagus is the most frequently involved region of the gastrointestinal tract.

Clinical features are mainly dysphagia and heartburn due to reflux oesophagitis caused by aperlistalsis and incompetent LES. 

Rings and webs 

1. Webs are mucosal folds in the upper esophagus above the aortic arch. 
2. Schatzki rings are mucosal rings at the squamocolumnarjunction below the aortic arch.
3. Plummer Vinson Syndrome consist of triad of dysphagia, atrophic glossitis, and anemia. Webs are found in the upper esophagus. The syndrome is associated specifically with iron deficiency anemia and sometimes hypochlorhydria. Patients are at increased risk for carcinoma of the pharynx or esophagus. 

Mallory-Weiss syndrome
Mallory-Weiss tears refers to small mucosal tears at the gastroesophageal junction secondary to recurrent forceful vomiting. The tears occur along the long axis an result in hematemesis (sometimes massive).

- Characterized by lacerations (tears) in the esophagus.
- Most commonly occurs from vomiting (alcoholics).
- A related condition, known as Boerhaave syndrome, occurs when the esophagus ruptures, causing massive upper GI hemorrhage.

Esophageal varices
- The formation of varices (collateral channels) occurs from portal hypertension.
Causes of portal hypertension include blockage of the portal vein or liver disease (cirrhosis).
- Rupture of esophageal varices results in massive hemorrhage into the esophagus and hematemesis.
- Common in patients with liver cirrhosis.

Diverticula 
are sac-like protrusions of one or more layers of  pharyngeal or esophageal wall. 

Tumors 
- Benign tumors are rare. 
- Carcinoma of the esophagus most commonly occurs after 50 and has a male:female ratio of 4.1. 

Etiology: alcohal ingestion, smoking, nitrosamines in food, achalasia , web ring, Barrettes esophagus, and deficiencies of vitamins A and C , riboflavin, and some trace minerals

Clinical features include dysphagia (first to solids), retrosternal pain, anorexia, weight loss, melena, and symptoms secondary to metastases. 

Pathology 

- 50% occur in the middle third of the esophagus, 30% in the lower third, and 20% in the upper third. Most esophageal cancers are squamous cell carcinomas. 
Adenocarcinomas arise mostly out of Barrett's esophagus.

Prognosis

is poor. Fewer than 10% of patients survive 5 years, usually because diagnosis is made at a late stage. The  most common sites of metastasis are the liver and lung. The combination of cigarette smoking and alcohol is particularly causative for esophageal cancer (over l00%  risk compared to nondrinkers/nonsmokers). 

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. 

Congestive heart failure (CHF)
A. Left-sided CHF

1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.

B. Right-sided CHF

1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.

ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

Blastomycosis (North American Blastomycosis; Gilchrist's Disease)

A disease caused by inhalation of mold conidia (spores) of Blastomyces dermatitidis, which convert to yeasts and invade the lungs, occasionally spreading hematogenously to the skin or focal sites in other tissues.

Pulmonary blastomycosis tends to occur as individual cases of progressive infection

Symptoms are nonspecific and may include a productive or dry hacking cough, chest pain, dyspnea, fever, chills, and drenching sweats. Pleural effusion occurs occasionally. Some patients have rapidly progressive infections, and adult respiratory distress syndrome may develop.