Opportunistic and Deep Mycoses

Coccidioides immitis  (Southwest USA)

• Located in desert soil
• Characteristic structures
• In the environment:  Arthroconidia
• In the body:  Sphereules are pathognomonic

Blastomyces dermatitidis  (north central and southeast USA)

• Associated with water

Lymphocutaneous Sporotrichosis

Mucocutaneous mycoses:  candida and dermatophytosis (get inflammatory response)

• Candida albicans
• Primary cutaneous candidiasis
• Mucocutaneous candidiasis

Candidiasis

• Wide range of infections
• Candida albicans is the most virulent species
• Candida spp. are common organisms of the skin, GI and UG tracts.
• Candidiasis is a disease of compromised hosts.

Mucocutaneous (T CELL IMPAIRMENT)

• Systems affected:
• GI tract, skin, vagina
• Onychomycosis
• Keratitis
• Symptoms:  Odynophagia, stridor, etc.
• Diagnosis: white pseudomembranous plaques with hyphae, pseudohyphae, and budding yeast.
• Groups at risk
• HIV patients
• Diabetics
• Pregnancy
• Age
• Antibiotics
• Steroids

Chronic mucocutaneous candidiasis – autoimmune polyendocrinopathy candidosis ectodermal dystrophy

• Inherited disorder of CMI to candida along with polyendocrinopathies
• Intractable candida infection of the mucocutaneous areas
• Concurrent adrenal insufficiency and hypoparathyroidism
• Type I diabetes
• Hypothryroidism
• Hypogonadism
• Ectodermal dystrophy

Deeply invasive candidiasis (think CANCER)

• Systems affected/ symptoms and signs:
• Candidemia
• Endocarditis – organism is sticky
• Hepatosplenomegaly
• Acute, shocklike syndrome
• Renal dysfunction

At risk groups:  

• Altered barriers
• Neutropenia
• Transplant
• Hemodialysis
• Pathogenesis
• Adherence and colonization
• Penetration through mucosal barriers and angioinvasions/access through catheters
• Hematogenous spread
• Replication yields necrosis +/- abscess with budding yeast and hyphae
• Look at the fundus!  Candida goes to the eyes!

Virulence factors of Candida

• Surface receptors
• Cell wall is an immune modulator
• Hydrolytic enzymes – e.g. acid protease, phospholipase
• Host mimicry – e.g. C3D receptor
• Dimorphism – makes it hardy!
• Germ tube + species.

Superficial:  

• Fungus confined to the stratum corneum or distal portions of hair
• Tinea versicolor:  Malassezia furfur
• Pigmentation changes due to fungal effect on melanocytes
• Can cause folliculitis
• Can cause fungemia in neonates with indwelling vascular catheters receiving total nutrition with lipids.
• Malassezia furfur is a lipophilic yeast and it requires fatty acids to grow.

Microscopic morphology of Aspergillus

Medical Mycology

• Microscopic morphology of Aspergillus fumigatus showing typical columnar, uniseriate conidial heads. Conidiophores are short, smooth-walled and have conical shaped terminal vesicles, which support a single row of phialides on the upper two thirds of the vesicle.

• Microscopic morphology of Aspergillus fumigatus showing typical columnar, uniseriate conidial heads. Conidiophores are short, smooth-walled and have conical shaped terminal vesicles, which support a single row of phialides on the upper two thirds of the vesicle.

• Microscopic morphology of Aspergillus niger showing large, globose, dark brown conidial heads, which become radiate, tending to split into several loose columns with age. Conidiophores are smooth-walled, hyaline or turning dark towards the vesicle. Conidial heads are biseriate with the phialides born on brown, often septate metulae. Conidia are globose to subglobose, dark brown to black and rough-walled 

• Microscopic morphology of Aspergillus flavus. Conidial heads are typically radiate, later splitting to form loose columns, biseriate but having some heads with phialides borne directly on the vesicle. Conidiophores are hyaline and coarsely roughened, often more noticeable near the vesicle. Conidia are globose to subglobose, pale green and conspicuously echinulate. Some strains produce brownish sclerotia. 

• Microscopic morphology of Aspergillus nidulans. Conidial heads are short columnar and biseriate. Conidiophores are usually short, brownish and smooth-walled. Conidia are globose and rough-walled.

• Grocott's methenamine silver GMS stained tissue section of lung showing fungal balls of hyphae of Aspergillus fumigatus in lung tissue, note conidial heads forming in an alveolus

• Grocott's methenamine silver GMS stained tissue section of lung showing fungal balls of hyphae of Aspergillus fumigatus

• Asperilloma found at post-mortem in the lung of a child with leukemia.  Note fungus ball occupying cavity

Vascular Pathology

Large vessels vasculitis

Medium vessels vasculitis

Small vessels vasculitis

Parathyroid Glands

Four in number : 2 superior & 2 inferior
6mm in length
30-50mg each

Location:

    a. Superior parathyroid- near the junction of inferior thyroid artery & rec. laryngeal nerve.
    b. Inferior parathyroid – situated in the lower pole

Blood Supply: 

  Branches of the inferior thyroid arteries.
  May also be supplied by: sup. thyroid artery
                                          thyroid ima artery
                                          laryngeal, tracheal & esophageal arteries.

Venous Drainage:

   Parathyroid veins drain into thyroid plexus of veins of the thyroid gland and trachea.


Lymphatic Drainage:
     Deep cervical & paratracheal L.N

Nerve Supply of parathyroid gland is derived from thyroid branches of cervical sympathetic ganglion.

DEVELOPMENT

• Superior parathyroid from fourth pharyngeal pouch
• Inferior parathyroid from third pharyngeal pouch
• Parafollicular cells from ultimobranchial body ( 4th pharyngeal pouch)

HISTOLOGY

-capsule
-cells present are: chief cell ( contain lipid)
                             oxyphil cell
                             stromal, connective tissue and fat.

FUNCTION

-PTH secretion : Calcium homeostasis

Primary hyperparathyroidism

a.Etiology

Parathyroid adenoma (80%); may be associated with MEN I and II
Parathyroid hyperplasia (15%):
Diffuse enlargement of four glands
Usually composed of chief cells
Parathyroid carcinoma (very rare)
Paraneoplastic syndrome: lung and renal cell carcinomas

b. Pathogenesis: excess production of parathyroid hormone (PTH) leads to hypercalcemia
 c.Clinical features
 Often asymptomatic
 Kidney stones
 Osteoporosis and osteitis fibrosa cystica
 Metastatic calcifications
 Neurologic changes

Secondary hyperparathyroidism

a. Etiology
i. Chronic renal failure
 ii. Vitamin D deficiency
iii. Malabsorption
b. Pathogenesis: caused by any disease that results in hypocalcemia, leading to
increased secretion of PTH by the parathyroid glands

Hypoparathyroidism

a. Etiology
i. Surgical removal  of glands during thyroidectomy
ii. Di George syndrome
 iii. Idiopathic
b. Clinical features
i. Lab: hypocalcemia
 ii. Neuromuscular excitability and tetany: Chvostek's and Trousseau's signs
iii. Psychiatric disturbances
iv. Cardiac conduction defects (ECG: prolonged QT interval)
T/t: Vit D & Calcium

Multiple Endocrine Neoplasia Syndromes (MEN)

 MEN syndromes

a. Autosomal dominant inheritance with incomplete penetrance
b. Characterized by hyperplasia and tumors of endocrine glands

2. MEN I (Werner syndrome)

a. Features tumors of the pituitary gland, parathyroids, and pancreas
b. Associated with peptic ulcers and the Zollinger-Ellison syndrome
c. Genetic mutation of MEN I gene

MEN II (lla or Sipple syndrome)
a. Features medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid
     hyperplasia or adenoma
b. Genetic mutation of RET proto-oncogene

MEN III (lIb)
a. Features medullary carcinoma of the thyroid, pheochromocytoma, and mucocutaneous neuromas
b. Genetic mutation of RET proto-oncogene.