Pathology Week 17 p31-41

7/30/2019 Pathology Week 17 p31-41

1/11

Acid-fast Stain ofM. tuberculosis:

Above: Cording virulent strains willcord (organisms wrap around each other)

Primary TB mid-lung fields, involvement of lymph nodes (Ghon complex) Reactivation/Secondary TB apices of lungs. Exaggerated more cavitation, necrosis, lymph node

involvement (because all the destruction is due to the immune response, and the patient has already been

exposed)

Ghon Complex or Primary Complex: Reactivation TB:

Ghon Complex: LN and peripheral lesion

Miliary tuberculosis (hematogenous spread): Granuloma with necrotic center:

Above (left): If organism gains entry into pulmonary artery, will shower into the lungs will get small affected areaseverywhere = Miliary TB. Everything that has been shown for TB can also be said for Histo can have MiliaryHistoplasmosis. Major difference is that TB is spread from person-to-person (communicable), Histo is not.Above (right):Necotizing granuloma seen in TB and Histo. If you have non-necrotizing granuloma, could besarcoidosis.

Upper lobe


2/11


3/11

Syphilis: Primary painless chancre Secondary rash on palms and soles; condyloma lata Tertiary aortitis, tabes dorsalis (broad-based ataxia), gummas Argyll Robertson pupil not reactive to light but constricts with accomodation Thoracic aorta aneurism

In all stages of syphilis, see endarteritis inflammation of blood vessels, surrounded by plasma cells

Aneurysm in the ascending aorta Many plasma cells present Spirochetes

Can see spirochetes at any stage of the disease if you do the right serology.

Syphilis serology: FTA- treponemal test is more specific, is positive earlier and persists for life VDRL- non-treponemal test- fades

VDRL+/FTA+ is infection VDRL+/FTA- is probably a false+ - see lots of this in pregnancy VDRL-/FTA+ is successful treatment

Candida: C. albicans - #1 pathogen in Candida infections; thrush (overgrowth in mouth or vagina); esophagitis; sepsis.

Yeasts and pseudohyphae in tissue and on cornmeal agar; germ tube+; chlamydoconidia+ C. tropicalis - yeast and pseudohyphae in tissue; fungemia

C. glabrata - yeast ONLY, no pseudohyphae Fluconizole, caspofungin *ALL Candidas FERMENT some sugars

Candida budding yeasts and pseudohyphae: C. albicans positive germ tube test:

Yeasts continue to bud and elongate.

Systemic Mycoses: Dimorphic Mold phase in nature and in lab at 23C Yeast or yeast-like phase in human tissue and at 37C (except cox) Some are endemic Infect ALL people

Most of the organisms that cause life-threatening infections in NORMALpeople are dimorphic fungi molds innature, yeasts in the body.


4/11

Systemic Mycoses (contd): Coccidioides immitis (cox)- endemic in desert SW, esp. SJ Valley in Ca. and in Az.; SPHERULES in tissue; mold

with arthroconidia in lab at room temperature Histoplasma capsulatum- intracellular small, budding yeast in tissue; mold with tuberculate/spiny macroconidia in

lab; blackbird, chicken and bat roosts

Grows in soil as a mold, makes arthroconidia (inhale), grows in body as a spherule w/endospores inside.

Spherules ofC. immitis: Arthroconidia ofC. immitis:

Endospores inside spherule Empty spherules endospores have broken out.

H. capsulatum yeasts in macrophage: H. capsulatum spiny/tuberculate macroconidia

About ~1/3 size of RBCs (uniquely small).

Mississippi River Valley endemic area for Histo Blasto endemic area is more SE. Pneumocystis everywhere.

Histoplasma black birds, chickens, bats. Get it from soilcontaminated w/bird and bat material.

Cryptococcus pigeon dung (but people who are around pigeonsdont get infected) seen everywhere. Dont really know wherepeople get it.

Coccidioidomycosis endemic area:

Grows as mold inlab big, spinymacroconidia.Identify w/DNAprobe, though,because growingtakes too long.


5/11

Systemic Mycoses (contd): Blastomyces dermatitidis- large yeast with Broad-Based-Buds and thick cell wall

in tissue; southeastern U.S.; skin hyperplasia (pseudoepitheliomatoushyperplasia) mimics carcinoma of skin and larynx.

o Blastomycosis skin lesions Pseudoepitheliomatous hyperplasia. Blastomycosis always starts as apulmonary infection. Will see broad-based buds and thick cell walls in

sputum or lung biopsy.o Broad-based buds ofBlastomyces dermatitidis

Paracoccidioides brasiliensis- mariners wheel in tissue; SouthAmerica only Treatment- AZOLES (eg. Fluconazole) prevents ergosterol synthesis;

AMPHOTERICIN B destroys ergosterol in the cell membrane;Echinocandin/CASPOFUNGIN inhibits glucan synthetase

Opportunistic fungi: Candida- yeasts and pseudohyphae

Seen in people who are immune-suppressed or gettingtherapy for malignancies.

Aspergillus septate hyphae; 45 degree branching; transplants Mucor aseptate hyphae; 90 degree branching; diabetic ketoacidosis Cryptococcus neoformans capsule (India Ink+, latex+); melanin+ ??pigeons??

Cryptococcus neoformans: Latex agglutination test: Septate hyphae ofAspergillus:

Use serum or spinal fluid. Sensitive and specific.

Neutropenic patients get Aspergillus infections. Also happens to diabetics. Septate hyphae, acute angle branching.

Aseptate hyphae ofMucororRhizopus: Rhizopus:

Above (left):Aspergillus appearance if grown in the lab. Fist-shaped structure w/bowling pins on top conidia on top.Hyphae are septate.Above (middle): Mucor primarily in diabetics. See broader hyphae. If you saw it in a smear, would see how ribbonythey are (curl up). Branch at 90 degrees; no cross-walls.Above (right): Rhizopus. Hyphae do not have septate, produce bags of sporangia. If it makes root-like structures, itsRhizopus. If the roots are off to the side, its Absidia (rare). No roots = Mucor.


6/11

Candida and Cryptococcus opportunistic yeasts. Aspergillus, Mucor opporutnistic hyphal fungi.

More fungi: Pneumocystis- fungus that cannot be cultured; trophozoites on Giemsa and cysts on GMS (silver); TMP-SMX,

pentamadine Sporothrix- dimorphic; thorn or rose prick; nodules along lymphatics; cigar/pencil-shaped yeast is classic;

potassium iodide

Pneumocystis fills alveoli on H&E stain: Pneumocystis cysts:

Bubbly pink filling in alveoli. Cysts show up on GMS stain. Trophozoites show up on Giemsa.

Pneumocystis cysts = round bodies that may have targets (bulls-eyes) on GMS. Sometimes see grooves, can look liketea-cups.

Pneumocystis trophozoites:


7/11

UTIs:o Community- E. coli 75%; Staphylococcus saprophyticus 20% (esp. sexually-active females)o Nosocomial- E. coli 40-50%; Proteus, Klebsiellao UTI- dysuria, frequency; WBC in urineo Pyelonephritis- fever, chills, flank pain; WBC casts in urine

STDs:o N. gonorrhoeaeo T. pallidum- painful chancre; condyloma lata and rash; gummaso HSV2 (70%)/HSV1(30%)- giant cells with glassy cytoplasm and Cowdry A inclusionso LGV- C. trachomatis serovas L1-L3o Trichomonas- vaginitis, strawberry mucosao HPV 6, 11- condyloma accuminata; koilocyteso HPV 16, 18 (and a dozen others) high risk for dysplasia/cervical cancero Haemophilus ducreyi- chancroid (soft chancre); painfull ulcer; school of fish on Gram staino Gardnerella vaginalis- vaginosis; clue cells; +whiff test

Condyloma lata ofT. pallidum: Herpes virus (H. simplex): CMV nuclear and cytoplasmic inclusions

Cowdry A inclusions

Above (left): Condyloma lata (syphilis). Remember condyloma accuminatum happens in HPV.Above (middle): Herpes Cowdry A inclusions (chromatin darker around edge). This is a Pap smear specimen.Above (right): CMV. Owls eye inclusion middle of nucleus. Outer part doesnt have any chromatin left. Cowdry Btype. Greatly enlarged cell.

Trichomonas vaginalis: Green smudges are T. vaginalis on Pap Stain: Condyloma accuminatum

Urethritis HPV

Koilocyte of HPV (usually low grade): Clue Cell ofGardnerella vaginalis:

Lower grade dysplasia (HPV 6, 11)

If patient has urethritisand you see epithelialcells coated w/bacilli(gram-negative rods) =Gardnerella vaginalis.


8/11

Nutrition Highlights:

MARASMUS: < 60% body weight Diet lacks protein & carbohydrate Loss ofmuscle mass (somaticprotein)- amino acids for energy Serum proteins (visceral compartment) NORMAL

o Especially albumin Loss of subcutaneous fat (broomstick) EMACIATION loss of BOTH muscle and fat

Head looks too big, abdomen not protuberant(because no ascites), no periorbital edema

SIGNS OF KWASHIORKOR loss of protein Flaky Paint Skin- hypo- and hyper-pigment and desquamation Hair loss or color change FATTY LIVER due to loss of apolipoproteins; also smallintestine

atrophy/disaccharidase deficiency and diarrhea Apathetic with LOSS OF APPETITE Multivitamin deficiencies** Immune defects and infections** Anemia- usually hypochromic/microcytic** Cerebral atrophy**

Pitting edema and ascites due to hypoalbuminemia

**both in MARASMUS AND KWASHIORKOR

ANOREXIA NERVOSA: Self-induced starvation Like PEM plus: Amenorrhea Hypothyroidism Scaly, yellow skin and lanugo Osteoporosis-like Anemia, lymphpenia, hypoalbuminemia HYPOKALEMIA AND CARDIAC ARYTHMIA

VITAMIN A DEFICIENCY: Night blindness Xerophthalmia (dry eye)- keratinized squamous epithelium replaces mucus-secreting epithelium Bitot spots (keratin debris) and keratomalacia (destruction of the cornea) Squamous metaplasia in LUNG (infections) and BLADDER (stones) Increased mortality in measles and diarrhea Also important in granulocyte maturation and in fallopian tubes.

Spots/lesions/destruction of cornea. See squamous metaplasia in kidney or lung. Corneal destruction.

Marasmus:

Kwashiorkorswollen abdomen(due to fatty liver);

periorbital edema

BULIMIA NERVOSA: < have amenorrhea

o Major difference between bulimia andanorexia

Weight and gonadotrophins near normal Hypokalemiaand CARDIAC ARYTHMIA Aspiration of gastric contents Mallory-Weiss Syndrome- laceration of the

esophagus or stomach Boerhaaves Syndrome- rupture of esophagus or

stomach


9/11

VITAMIN A TOXICITY: Increased intracranial pressure Papilledema, headache, vomiting Bone pain and hypercalcemia

VITAMIN D DEFICIENCY: HYPOCALCEMIA and loss of bone: RICKETS (kids) or

OSTEOMALACIA (adults) Robbins Figure 9-29 lists causes of Rickets and

Osteomalacia:1. < diet or sunlight2. pancreatic insufficiency or obstruction3. drugs, liver disease, renal disease4. phosphate depletion

In rickets and osteomalacia there is an excess ofUNMINERALIZED matrix

In children (rickets) endochondral bone growth is alsodisturbed

Problem is w/mineralization. Have plenty of osteoid (Vitamin C deficiency is opposite).

RICKETS: Osteoid with inadequate mineralization Disorganized fibroblasts and capillaries Microfractures Deformed bones Abnormally-shaped (square) head, rachitic rosary (rib formation), pigeon breast, and

bowed legs

OSTEOMALACIA: Abnormal bone remodeling Inadequate mineralization of new bone Fractures and microfractures Vertebrae and femoral neck Note: osteoporosis is caused by inadequate osteoid protein and

defective Vit D receptors w/ demineralization

Vitamin D Deficient Normal

Figure: Normal bone vs.Osteoporosis vs. Osteomalacia

Osteomalacia total volume is similar tonormal bone.

Osteoporosis lose volume of bone

Rickets


10/11

Vitamin D Antimicrobial Effect: Toll-like Receptors (TLRs) Increase in Vitamin D receptor Synthesis ofCathelicidin Inhibition of M. tuberculosis

VITAMIN K: Deficiency = Bleeding, especially intracranial in infants; also bleeding umbilical stump Vitamin K factors: Factors II, VII, IX, X, Protein C and S Cryoprecipitate is not a good source of these Vitamin K factors. If patient is Vitamin K deficient, do not want to

give cryo + Vitamin K. Want to give Vitamin K + FFP

Vitamin A important in lung (defense against viral and bacterial infections) Vitamin D defense against M. tuberculosis Vitamin C important in wound healing, so deficiency improper collagen development/wound healing (especially in

oral cavity)

THIAMINE: Not in polished rice, white flour or refined sugar TPP is a cofactor in oxidative decarboxylation and deficiency of thiamine

results in DECREASED ATP Cardiovascular and nervous system problems of all alcoholics are thiamine deficient

THIAMINE DEFICIENCY: Dry beriberi (polyneuropathy)- myelin degeneration Wet beriberi (cardiovascular)- vasodilitation produces heart failure and

edema Wernicke-Korsakoff Syndrome- Wernicke ataxia/confusion; Korsakoff

amnesia, confabulation

NIACIN: Below: Skin lesions of pellagra. NAD and NADP are coenzymes for dehydrogenases Grains, legumes and seed oils Deficiency- PELLAGRA (3 Ds): dermatitis, diarrhea (epithelial

atrophy) and dementia (posterior column changes as in B-12deficiency)

NIACIN AND HEART DISEASE: High doses (1-6 grams per day) Lowers LDL Lowers triglycerides Increases HDL

VITAMIN C (ASCORBIC ACID): (Citrus) fruits and vegetables Bone disease in growing children Hemorrhage and poor wound healing in children and adults Vitamin C is a cofactor in formation and maturation of procollagen Hydroxylation is impaired and crosslinks are not formed Antioxidant???

VITAMIN C DEFICIENCY: SCURVY Capillary and venule walls are weak with hemorrages (purpura and ecchymoses) Trauma hematoma and hemarthrosis (joints as in hemophilia) Child- too much cartilage and not enoughosteoid protein); bowed legs and deformed chest Bacterial infection associated with gingival hemorrhage


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Pathology Week 17 p31-41