Systemic Pathology Flashcards
What are Teratogens?
Teratogenesis
- Induction of nonhereditary congenital malformation (birth defects) in a developing fetus by exogenous factors:
- Physical
- Chemical
- Biologic agents
- Teratogens = Teratogenic agents
-
Maternal infection
-
TORCH complex:
- Toxoplasmosis, Other agents, Rubella, CMV (cytomegalovirus) and HSV (Herpes Simplex Virus)
-
TORCH complex:
- Physical agents
- Radiation
- Hypoxia
- CO2
- Mechanical trauma
- Hormones:
- Sex hormones
- Corticosteroids
- Sex hormones
- Vitamine deficincies
- Riboflavin
- Naicin
- Folic acid
- Vitamin C
- Drugs
- Mitomycin
- Dactinomycin
- Puromycin
What are the effects of teratogens, Mechanism of action, and susceptibility
Teratogenesis
-
Effects of teratogens:
- Death
- Growth retardation
- Malformation
- Functional impairment
-
Mechanism of teratogens
- Specific for each teratogen: inhibit, interfere, or block metabolic steps critical for normal morphogenesis
- Most are site or tissue-specific
-
Susceptibility to teratogens is :
- Variable
- Specific for each developmental stage
- Dose-dependent
Name the Autosomal Abnormalities (chromosomal)
Down syndrome
Edward syndrome
Patau syndrome
What is Down syndrome?
Autosomal Abnormality
Down Syndrome
- Chromosomal Abnormality: Trisomy 21
- Findings:
- Mental retardation
- Epicanthal folds
- Large protruding tongue
- Small head
- low-set ears
- Broad flat face
- Simian crease
- Complications
- Increased leukemia
- Increased infection
- Alzheimer-like brain change
Down syndrome is the most frequent chromosomal disorder (1:700 births). People with down syndrome can live into their 30s and 40s.
What is Edward syndrome?
Autosomal Abnormality
Edward syndrome
- Chromosomal Abnormality: Trisomy 18
- Findings:
- Mental retardation
- Small head
- Micrognathia (small lower jaw)
- Pinched facial appearance
- Low-set, malformed ears
- Rocker bottom feet
- Heart defects
- Prognosis: Months
Second most incidence: 1:3000
What is Patau Syndrome?
Autosomal Abnormality
Patau Syndrome
- Chromosomal Abnormality: Trisomy 13
- Findings:
- Mental retardation
- Microcephaly (Small head)
- Microphthalmia (small eye)
- Brain abnormalities
- Cleft lip and palate
- Polydactyly
- Heart defects
- Prognosis: < 1 yr
Least likely of the three autosomal abnormalities to occur
Name and describe the two types of Sex chromosome abnormalities
Sex Chromosome Abnormalities
Klinefelter Syndrome
- Chromosomal Abnormality: XXY
- Findings:
- 1:500 men
- Manifests at puberty
- Hypogonadism, atrophic testes
- Tall stature
- Gynecomastia
- Female pubic hair distribution
- Low IQ
- Associated with increased material and increased paternal age
Turner Syndrome
- Chromosomal Abnormality: XO
- Findings:
- 1:3000 live female births
- Diagnose at birth or puberty
- Female hypogonadism
- Primary amenorrhea
- Short Stature
- Webbed neck
- Wide-spaced nipples
- Coarctation of aorta
What are Lysosomal Storage Diseases
Lysosomal Storage Diseases
- Are common in people of Eastern European ancestry
- Diseases include:
- X-linked
- Fabry
- Hunter’s
- Autosomal Recessive
- Tay-Sachs
- Gaucher
- Niemann-pick
- X-linked
Explain Cystic Fibrosis
Childhood Genetic Disorder
Cystic Fibrosis
- Most common fatal genetic disease in white children
- Due to the deletion causing loss of phenylalanine at position 508 in the CFTR gene
- Occurs in both males and females (M = F)
- Life expectancy = 28 yrs
- Generalized exocrine gland dysfunction. Problem with Cl- transporter
- Multiple organ systems
- Characterized by respiratory and digestive problems
-
Pathogenesis: Chromosome 7q
- Gene encodes CFTR (cystic fibrosis transmembrane regulator)
- Regulates Cl- and Na+ transport across epithelial membranes
- Affects Na+ channels, especially mucous and sweat glands
- Tests: Sweat chloride test
-
Findings:
- Chronic pulmonary disease
- From thick mucous in airways
- Lung infections (bronchiectasis)
- Bronchiectasis
- From thick mucous in airways
- Pancreatic exocrine insufficiency
- Meconium ileus
- Intestinal obstruction in infants/newborns
- Chronic pulmonary disease
What is von Hippel-Lindau Disease
Childhood Genetic Disorder
von Hippel-Lindau Disease
- Autosomal Dominant
- Chromosome 3
- VHL gene
- Findings
-
Hemangiomas (bloody red birthmark)
- Retina
- Cerebellum
-
Hemangiomas (bloody red birthmark)
- Cysts and adenomas
- Liver
- Kidney
- Adrenal glands
- Pancreas
What is Marfan’s syndrome
Childhood Genetic Disorder
Marfan’s Syndrome
- Uncommon hereditary connective-tissue disorder
- Fibrillin gene mutation
-
Findings:
- Skeletal
- Tall and thin patients
- Abnormally long legs and arms
- Spiderlike fingers
- Cardiovascular
- Cystic medial necrosis of aorta
- Risk aortic incompetence, dissecting aorta aneurysm
- Distensible mitral valve
- Cystic medial necrosis of aorta
- Ocular: Lens dislocation
- Skeletal
State the two Hypopigmentation disorders of the skin and explain
Hypopigmentation Disorders
Albinism
- Failure in pigment production from otherwise intact melanocytes
- usually tyrosinase problem; can’t convert tyrosine to DOPA (in the pathway to form melanin)
Vitiligo
- Acquired loss of melanocytes
- Discrete areas of skin with depigmented white patches
- May be autoimmune
State the disorders associated with Hyperpigmentation
Hyperpigmentation
- Freckle (ephelis): increased melanin pigment within basal keratinocytes
- Lentigo: Pigmented macule caused by melanocytic hyperplasia in epidermis
- Pigmented nevi (benigh - nonneoplastic) skin lesion
- Lentigo maligna (benign - nonneoplastic) skin lesion
-
Cafe au lait spots
- Increase in melanin content with giant melanosomes
- Conditions with cafe au lait spots include:
- Neurofibromatosis type I (most frequent neurocutaneous syndrome)
- McCune - Albright syndrome (Fibrous dysplasia)
- Tuberous sclerosis (rare disease that causes nonmalignant tumors in the brain and organs)
- Fanconi anemia (rare disease resulting in loss of DNA repair with increased risk of cancer and endocrine problems)
-
Diffuse hyperpigmentation with Addison’s disease (too little cortisol)
- Secondary to increased melanocyte-stimulating hormone
State the type of Viral Skin Eruptions
Viral Skin Eruptions
- Molluscum contagiosum (Poxvirus)
- Verruca vulgaris (common wart) (Human papilloma virus (HPV))
- Herpes simplex
- Roseola (exanthema subitum) (herpes virus 6 and 7)
- Rubella
- Measles (rubeola) (paramyxovirus)
Describe Impetigo
Etiology
Signs/symptoms
Treatment
Course/prognosis
Impetigo
-
Common skin infection
- Common in preschool age children (2-5 yrs old)
- Especially during warm weather
-
Etiology
- Invasion of epidermis by staphylococcus aureus or Streptocuccus pyogenes
- Similar to cellulitis, but more superficial
- Highly infectious
-
Signs/symptoms
- Starts as itchy, red sore
- Blisters -> breaks -> oozes
- Ooze dries; lesion becomes covered with a tightly adherent crust
- Grows and spreads circumfrentially (no deep); rarely impetigo forms deeper skin ulcers
- Contagious; carried in the oozing fluid
-
Treatment
- Topical antimicrobial (eg. bactroban)
- Oral antibiotic (erythromycin or dicloxacillin) rapid clearing of lesions
-
Course/prognosis
- Impetigo sores heal slowly and seldom scar
- Cure rate is extremely high
- Recurrence is common in young children
Note: Acute glomerulonephritis (renal disease) is an occasional complication (poststreptococcal glomerulonephritis (GMN))
Name the immunologic Skin Lesions
Immunologic Skin Lesions
Hives
Pemphigus Vulgaris
Bullous Pemphigoid
Erythema Multiforme
Steven-Johnson Syndrome
Toxic Epidermal Necrolysis
Explain the immunologic Skin Lesions
Hives
immunologic Skin Lesions
Hives
- Urticaria = wheals
- Type I hypersensitivity
Explain the immunologic Skin Lesions
Pemphigus Vulgaris
immunologic Skin Lesions
Pemphigus Vulgaris
- Ages 30-60
-
Clinical
- Oral mucousal lesions (often first sign)
- Skin lesion follow
- Bullae rupture, leaving raw surface susceptible to infection
-
Etiology
- Autoimmune: IgG antibodies against desomsome protein
-
Histology:
- Formation of interdermal bullae
- Acantholysis: Tzanck cells
- Basal layer intact
- Formation of interdermal bullae
- Immunofluorescence show encircling of epidermal cells
What are Tzanck cells?
Tzanch cells
Multinucleate giant cells caused by a variety of skin pathologies
Explain the immunologic Skin Lesions
Bullous Pemphigoid
Bullous Pemphigoid
- Resembles pemphigus vulgaris
- Clinically less severe
-
Etiology
- Autoimmune: IgG antibodies against hemidesmosome proteins
-
Histology
- Subepidermal bullae
- Characteristic inflammatory infiltrate of eosinophils in surrounding dermis
- Immunofluorescence shows linear band
What is the main difference between Pemphigus vulgaris and Bullous pemphigoid
-
Pemphigus vulgaris
- Intraepidermal bullae
- More superficial
- Intraepidermal bullae
-
Bullous pemphigoid
- Subepidermal bullae
- Deep under epidermis
- Subepidermal bullae
Explain the immunologic skin lesion
Erythema Multiforme
immunologic skin lesion
Erythema Multiforme
- Peak incidence second and third decades
- Etiology
- Type III hypersensitivity
- Response to:
- Medications
- Sulfa drugs
- penicillin
- Barbiturates
- Infection
- HSV
- Hycoplasma
- Other illnesses
- Medications
- Damage to blood vessels of skin (because of immune complexes)
- Clinical
- Classic “target”, “bull’s-eye” or “iris” skin lesion
- Central lesion surrounded by concentric rings of pallor and redness
- Dorsal hands
- Forearms
- No systemic symptoms
- Classic “target”, “bull’s-eye” or “iris” skin lesion
What are the following immunologic skin lesions
- Steven-Johnson Syndrome
- Toxic Epidermal Necrolysis
immunologic skin lesions
1. Steven-Johnson Syndrome
- Variant, more severe form of erythema multiforme
- Severe systemic symptoms
- Extensive skin target lesions
- Involve multiple body areas, especially mucous membranes
2. Toxic Epidermal Necrolysis
- Also called TEN syndrome and Lyell’s syndrome
- Multiple large blisters (bullae) that coalesce, sloughing of all or most of the skin and mucous membranes
Name and describe the Benign (Nonneoplastic) skin lesions
Benign (Nonneoplastic) skin lesions
-
Acanthosis Nigricans
- Cutaneous finding of velvety hyperkeratosis and pigmentation
- Flexural areas, most often (axilla, nape of nex, flexures, Anogenital region)
- Often a marker of visceral malignancy (>50% have cancer: Gastric carcinoma, Breast, lung, uterine cancer)
- Seen in diabetes
- Histology:
- Acanthosis, Hyperkeratosis, Hyperpigmentation
- Cutaneous finding of velvety hyperkeratosis and pigmentation
-
Hemangioma
- Hamartoma (not ture neoplasm)
- Disorganized growth composed of tissue normally found in a given location
- Hamartoma (not ture neoplasm)
-
Xanthoma
- Associated with hypercholesterolemia
- Clinical
- Most common site:
- Eyelids (xanthelasma)
- Nodules over tendons or joints
- Histology
-
Yellowish papules or nodules composed of
- Focal dermal collections of lipid-laden histiocytes
-
Yellowish papules or nodules composed of
- Most common site:
What is the difference between hamartoma and choristoma?
Hamartoma = disorganized growht composed of tissue normally found in a given location
Choristoma = growth composed of histologically normal tissue found at a site where it is not normally found in the body
Explain Edema and how it is caused
Edema
- Abnormal accumulation of fluid in intestinal spaces or body cavities
- Fluid moves out of intravascular space
- Results from some combination of:
- Increased capillary permeability (with histamine)
- Increased capillary hydrostatic pressure
- Increased interstitial fluid colloid osmotic pressure
- Decreased plasma colloid osmotic pressure
Name and describe the two types of Edema
Edema
- Types of Edema:
-
Transudate
- More watery (serious) edema fluid
- Usually noninflammatory
- From altered intravascular hydrostatis or osmotic pressure
-
Exudate
- More protein-rich edema fluid
- usually inflammatory
- From increased vascular permeability (with inflammation)
-
Transudate
Name and describe examples of Transudate
Examples of Transudate
- Anasarca: Generalized edema
- Hydrothorax: Excess serous fluid in pleural cavity
- Hydropericardium: Excess watery fluid in pericardial cavity
- Ascites (hydroperitoneum): Excess serous fluid in peritoneal cavity (stomach)
What does Right-sided conjestive heart failure lead to vs. Left-sided conjestive heart failure?
-
Right-sided conjestive heart failure
- results in peripheral edema
-
Left-sided conjestive heart failure
- results in pulmonary edema
What are examples of Edemas and causes
Edemas and causes
-
Congestive Heart Failure
- Increase in plasma/capillary hydrostatic pressure
-
Nephrotic syndrome
- Decrease in plasma oncotic pressure
-
Cirrhosis
- Increase in capillary hydrostatic pressure
- Decrease in plasma oncotic pressure
-
Elephantitis
- Increase in plasma/capillary hydrostatic pressure
- Secondary to decrease lymphatic return
What is Shock
Shock
Decreased cardiac output is the major factor in all types of shock (because either decrease HR, decrease Stroke Volume, or both)
- Decrease tissue perfusion
- Hemodynamic changes result in
- Decrease blood flow, thereby
- Decrease oxygen and metabolic supply to tissue
- Can result in multiple organ damage or failure
- Symptoms
- Fatigue
- Confusion
- Signs
- Cool pale skin (pallor)
- Weak rapid pulse (tachycardia = icncrease HR)
- Decrease BP (hypotension)
- Decrease urine output
- Shock requires immediate medical treatment and can worsen rapidly
What are the Major categories of shock
and describe
Major Categories of Shock
-
Hypovolemic
- Decrease blood volume
- Ex: Hemorrhage, Dehydration, Vomiting, Diarrhea
- Decrease blood volume
-
Cardiogenic
- Pump failure, Usually Left ventrical failure, Sudden decrease in Cardiac Output
- Ex: Massive MI, Arrhythmia
- Pump failure, Usually Left ventrical failure, Sudden decrease in Cardiac Output
-
Distributive
-
Septic
- Infection (endotoxin release), Gram negative bacteria, Causes vasodilation
- Ex. Severe infection
- Infection (endotoxin release), Gram negative bacteria, Causes vasodilation
-
Neurogenic
- CNS injury, Causes vasodilation
- Ex. CNS injury
- CNS injury, Causes vasodilation
-
Anaphylactic
- Type I hypersensitivity, Histamine release, Vasodilation
- Ex. Anaphylactic allergic reaction (insect sting)
- Type I hypersensitivity, Histamine release, Vasodilation
-
Septic
Name and decribe the three stages of shock
Stages of Shock (decreased blood flow)
-
Nonprogressive (early)
- = compensated
- Increase sympathetic NS
- Increase Cardiac Output
- Increase Total periferal resistance
- Try to maintain perfusion to vital organs
-
Progressive
- Decrease cardiac perfusion
- Cardiac depression
- Decreased Cardiac output
- Metabolic acidosis (Compensatory mechanism are no longer adequate)
-
Irreversible
- Organ damage
- Decrease high energy phosphate reserves
- Death (even if blood flow is restored)
Describe Congestion (Hyperemia) and its types
Congestion (Hyperemia)
- Increased volume of blood in local capillaries and small vessels
- Active congestion (active hyperemia) increased arteriolar dilation (inflammation, blushing)
-
Passive congestion (passive hyperemia): decreased venous return (obstruction, increased back pressure)
- Two forms:
- Acute
- Shock or right sided heart failure
- Chronic
- In lungs (usually secondary to left sided heart failure)
- In liver (usually secondary to right sided heart failure)
- Acute
- Two forms:
What is Thrombosis
What is the difference between Arterial and Venous Thrombi
Thrombosis
- Blood clot attached to endothelial surface (blood vessel or heart - endocardium)
- usually a vein
- Virchow’s triad
-
Arterial thrombi
- Lines of Zahn (morphologically)
- Alternating red and white laminations
-
Venous Thrombi
- Propagate: enlarge while remaining attached to vessel wall
- Embolize
- Detach as large embolus
- Fragment off as many small emboli; shower emboli
What is the Virchow’s Triad for Thrombosis
Virchow’s Triad for Thrombosis
- Endothelial injury
- Alteration in blood flow
- Hypercoagulability of blood
What are the Lines of Zahn for Arterial thrombi?
Lines of Zahn (arterial thrombi)
- White (fibrin and platelet) layers alternating with dark (RBC) layers
- Indicated thrombosis in aorta or heart before death