infectious and parasitic disease

2nd Year Pathology 2010

Infectious and Parasitic disease


Topics

Types of organisms. Host barriers to organisms. Methods of invasion by organisms. Types of response they cause within the

body. Organisms by system.


Classification of organismsViruses Bacteria Fungi

Nucleic acids DNA or RNA DNA or RNA DNA or RNA

Nuclear membrane

No No Yes

External cell wall

No Yes Yes

Antibiotic sensitivity

No Yes No

Replication Within host cells (can’t replicate themselves)

Within and outside host cells by binary fission

Within and outside host cells by binary fission and sexually


Classification of bacteria

1. Gram positive Rods (bacilli) Cocci

2. Gram negative

- Can be further divided into anaerobic and aerobic


Classification of viruses

1. DNA

2. RNA

Further classification: Single or double

strand Envelope on no

envelope


Host barriers to organisms

Intact skin Mucosal surfaces Their secretory and excretory products

Lysozyme secreted by tear glands Acid gastric juice


Defenses in gut

Acid gastric juice. Viscous mucous layer covering gut. Lytic pancreatic enzymes and bile

detergents. Secreted IgA antibodies.


Modes of transmission

Aerosol Mucosal contact Bloodstream Placental-foetal route


How microorganisms cause disease

1. Contact or enter host cells and directly cause cell death.

2. Release endotoxins or exotoxins that kill cells.

3. Induce host cellular responses that are directed against invader but cause additional host damage such as scarring and hypersensitivity reactions.


Special techniques for diagnosing infectious agents

Gram stain Most bacteria

Acid-fast stain Mycobacteria, nocardiae

Silver stains Fungi, legionellae, pneumocystis

Periodic acid-Schiff Fungi, amoebae

Mucicarmine Cryptococci

Giemsa Campylobacteria, leishmaniae, malaria parasites

Antibody probes Viruses, rickettsiae

Culture All classes

DNA probes Viruses, bacteria, protozoa


Inflammatory responses to infection

5 major patterns1. Suppurative inflammation

2. Mononuclear and granulomatous inflammation

3. Cytopathic-cytoproliferative inflammation

4. Necrotising inflammation

5. Chronic inflammation and scarring


Suppurative Inflammation Production of large amounts of pus

Comprised of: Neutrophils (attracted by chemoattractants generated by bacteria) Necrotic cells Oedematous fluid

Certain organisms (Staphylococcus) localised suppuration – pyogenic e.g. acute appendicitis

Abscess = focal, localised collection of purulent inflammatory tissue

Bacteria also attract neutrophils by releasing endotoxins that stimulate macrophages to release IL-1 or TNF


Mononuclear and granulomatous inflammation

Diffuse, predominantly mononuclear infiltrate in response to viruses, intracellular bacteria, spirochetes, intracellular parasites or helminths.

Occurs when aggregates of altered macrophages form around necrotic focus or fuse to form giant cells. e.g. M. tuberculosis


Cytopathic, cyto-proliferative inflammation

Characteristic of viral mediated damage in absence of host inflammatory response.

Viral particles may be visible as inclusions or cause cells to fuse (e.g. measles, herpesviridiae)

Can stimulate epithelial cells to proliferate (e.g. warts)


Necrotising Inflammation

Organisms that secrete toxins (e.g. Clostridium perfringens) cause rapid and severe tissue damage.

Cell death is predominant feature Resemble ischaemic necrosis in appearance

Disruption of nuclear staining and preservation of cellular outlines.


Chronic Inflammation and scarring

Final common pathway of many infections Leads to healing or extensive scarring

Can see similar pattern in response to physical or chemical agents


Acute Inflammation

Acute inflammation is marked by an increase in inflammatory cells.

Perhaps the simplest indicator of acute inflammation is an increase in the white blood cell count in the peripheal blood, here marked by an increase in segmented neutrophils (PMN's).


Seen here is vasodilation with exudation that has led to an outpouring of fluid with fibrin into the alveolar spaces, along with PMN's. The series of events in the process of inflammation are:

1. Vasodilation: leads to greater blood flow to the area of inflammation, resulting in redness and heat.

2. Vascular permeability: endothelial cells become "leaky" from either direct endothelial cell injury or via chemical mediators.

3. Exudation: fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly

4. Vascular stasis: slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to the stimulus.


Acute inflammation

The PMN's seen here are in alveoli, indicative of an acute bronchopneumonia of the lung. The PMN's form an exudate in the alveoli. This patient had a "productive" cough because large amounts of purulent sputum were produced. The source, the neutrophilic alveolar exudate, is seen here.


Here is an example of the fibrin mesh in fluid with PMN's that has formed in the area of acute inflammation. It is this fluid collection that produces the "tumor" or swelling aspect of acute inflammation.


A purulent exudate is seen beneath the meninges in the brain of this patient with acute meningitis from Streptococcus pneumoniae infection. The exudate obscures the sulci.

Chronic inflammation is more difficult to understand, because it is so variable. Seen here is chronic endometritis with lymphocytes as well as plasma cells in the endometrial stroma. In general, the inflammatory infiltrate of chronic inflammation consists mainly of mononuclear cells ("round cells"): lymphocytes, plasma cells, and macrophages.


This is a case of viral hepatitis C which is at a high stage with extensive fibrosis and progression to macronodular cirrhosis, as evidenced by the large regenerative nodule at the center right.

The screening laboratory test for this form of viral hepatitis is the hepatitis C antibody test. Hepatitis C accounts for most (but not all) cases formerly called "non-A, non-B hepatitis". In addition to this serologic test PCR and genotyping can be performed.


This is a healing biopsy site on the skin seen a week following the excision.The skin surface has re-epithelialized, and below this is granulation tissue with small capillaries and fibroblasts forming collagen. After a month, just a small collagenous scar will remain.

Cellular interactions with chronic inflammation


There is a small tan-yellow subpleural granuloma in the mid-lung field on the right. In the hilum is a small yellow tan granuloma in a hilar lymph node next to a bronchus. This is the "Ghon complex" that is the characteristic gross appearance with primary tuberculosis. In most persons, the granulomatous disease will not progress. Over time, the granulomas decrease in size and can calcify, leaving a focal calcified spot on a chest radiograph that suggests remote granulomatous disease.


The Ghon complex is seen here at closer range. Primary tuberculosis is the pattern seen with initial infection with tuberculosis in children. Reactivation, or secondary tuberculosis, is more typically seen in adults.


Here are two pulmonary granulomas. Granulomatous inflammation typically consists of mixtures of cells including epithelioid macrophages, giant cells, lymphocytes, plasma cells, and fibroblasts. There may even be some neutrophils.


Giant cells are a "committee" of epithelioid macrophages. Seen here are Langhans type giant cells in which the nuclei are lined up around the periphery of the cell. Additional pink epithelioid macrophages compose most of the rest of the granuloma.


This is an acid fast stain of Mycobacterium tuberculosis (MTB). Note the red rods--hence the terminology for MTB in histologic sections or smears: acid fast bacilli.


Two foreign body giant cells are seen just to the right of center where there is a bluish strand of suture material from a previous operation.


This is cytomegalovirus (CMV) infection in the lung. Note the very large cells that have large violet intranuclear inclusions with a small clear halo. Basophilic stippling can be seen in the cytoplasm.


An acute duodenal ulcer


The strongest association with Helicobacter pylori is with duodenal peptic ulceration--over 85% of duodenal ulcers. Seen here is a penetrating acute ulceration in the duodenum just beyond the pylorus.


Gastritis is often accompanied by infection with Helicobacter pylori. This small curved to spiral rod-shaped bacterium is found in the surface epithelial mucus of most patients with active gastritis. The rods are seen here with a methylene blue stain.


This yellow-green exudate on the surface of an inflamed, hyperemic (erythematous) bowel mucosa consists of many neutrophils along with fibrin and amorphous debris from dying cells.


Budding cells with pseudohyphae seen here are characteristic for Candida infection.


With a PAS stain, the budding cells and pseudohyphae (short filaments that are not true hyphae) of Candida stain bright red.


Herpes simplex

This is a microscopic section from the edge of one of a group of small round clear vesicles on the skin, just above the lip. Notice the mauve to pink homogenous intranuclear inclusions in the epithelial cells of the epidermis. This is typical for Herpes simplex virus (HSV) infection. The most common sites for Herpes simplex virus infections (either primary or reactivation) are skin and mucus membranes. HSV type I is seen most often in oral cavity, while HSV type II is more commonly a sexually transmitted disease.


By electron microscopy, viral particles of any herpesvirus appear as arrays and scattered single particles as shown here in a nucleus of a neuron from the cerebrum from a patient with herpes simplex encephalitis. Herpesviruses are large encapsulated viruses that contain double-stranded DNA in the nucleocapsid surrounded by the viral envelope.


This is Cryptococcus neoformans infection of the lung. There are numerous organisms that have a large mucoid capsule, giving the appearance of a clear zone around a faint round nucleus.


This is a Cryptococcus neoformans meningitis stained with GMS to reveal the nuclei. In this AIDS patient, the organisms didn't even bother to make a capsule. The budding cells of Cryptococcus have a narrow base.


Cryptosporidium

The little blue organisms lined up along the brush border of the small intestinal epithelium are Cryptosporidium parvum organisms causing the disease cryptosporidiosis. This infection may cause a mild diarrhea in immunocompetent persons but more severe illness in immunocompromised hosts.


Cryptosporidium parvum

Coccidian protozoan parasite. Causes watery diarrhoea in normal children. Chronic debilitating diarrhoea in patients with

AIDS. Not killed by chlorine. Adhere to intestinal and colonic epithelial

cells.


Giardia lamblia

Most prevalent pathogenic intestinal protozoan worldwide.

Infection may be subclinical or may cause acute or chronic diarrhoea.

Not killed by chlorine. Reside in duodenum. Adhere to but do not invade intestinal

epithelial cells.


Histoplasma - fungus


Histoplasma


Coccidomycosis - fungus


This is a scabies mite. The official name is Sarcoptes scabiei. These little organisms burrow in the epidermis, usually on the hands but sometimes elsewhere, and produce itching along the linear burrows. These lesions are often excoriated because of the itching.


Lice are arthropods of the class Insecta which generally inhabit hair and bite the human host for a blood meal. At the left is the head louse (Pediculus humanis capitis) and at the right is the crab (pubic) louse (Phthirus pubis).


Pneumocystis carinii

A ubiquitous organism, thought to be a fungus. Produces no disease in normal individuals. Severe pneumonia in most patients with AIDS and

in children with protein-calorie malnutrition. Alveolar air spaces filled with pink, foamy

amorphous material composed of proliferation parasites and cell debris.


Malaria - Plasmodium falciparum


These red blood cells, shown in a coloured electron micrograph, are infected with malarial parasites.

The parasites swell the cells and eventually break out and spread, infecting additional cells.

The more blood cells infected, the more severe the disease.


(a) Example of sequestration. Fresh coronal section of brain is swollen and slightly grey in colour, and has no visible haemorrhages. Bottom left, high-power (x100) view of cortex showing many parasitized vessels. Bottom right, single cortical vessel (under oil immersion (x1,000) containing unpigmented parasites.

(b) Pattern of sequestration and microvascular pathology. Fixed coronal section of brain is swollen and has multiple petechial haemorrhages in the cortical white matter. Bottom left, high-power (x400) view of cortex showing haemorrhage surrounding a parasitized vessel. Bottom right, higher-power (x400) view of cortex showing ring haemorrhage around vessel containing parasites and a thrombus.