Physiologic Changes in Pregnancy

Physiologic Changes in Pregnancy
By:Thomas S. Ivester, MD, MPH
Maternal-Fetal Medicine

Relevance of OB physiology
* 5-10 % of women in ER are pregnant
o Many don’t know or show
* Any female of reproductive age could be pregnant
o Should be assumed so!
* Virtually every organ system affected
* Can touch almost any specialty

Case history
Case 1

* 36 y.o. female presents to ER
* CC: Fatigue, dyspnea, chest pain
* HPI:
o Progressive SOB and dyspnea over several weeks.
o Poor exercise tolerance and easy fatigability
+ ‘get winded after 1 flight of stairs’
o Substernal chest pain, peaks in morning and night
o Nocturnal cough, semi-productive – clear
o Leg swelling
o polyuria
* PMH
o Mild obesity
* Ob/gyn – menses at age 12; irregular menses; no pregnancies
* Meds
o Oral contraceptives
o multivitamins
* Social
o Married for 2 years. No exposures

Case 1: PE
* Skin
o warm, clammy. Mild facial acne and increased hair – medium coarseness
* HEENT
o NC/AT. Nasal mucosa slightly hyperemic.
o Mild non-nodular thyromegaly
* CV
o Tachycardia (HR 107)
o + JVD
o 2/6 systolic murmurs over pulmonic and aortic v.
* Chest
o Clear bilaterally. Diaphragm elevated with decreased excursion
* Ext
o 1+ pretibial pitting edema
* Abd
o Skin – spider angiomata and striae. Medium course hair, infraumbilical.
o Distended, firm, non-tender.

Studies / labs
* EKG:
o Sinus rhythm; tachy; Left axis deviation
* CXR:
o Lungs clear. Cardiomegaly. Increased vascular markings
* Labs:
o Hct 32% (low); WBC 12 (high)
o Cholesterol 300 mg/dl
o D-dimer elevated
o Potassium and creatinine low

What does she have???
General Principles
* Most changes begin early
o Even before pregnancy recognized
* Most are hormonally driven
o Progesterone, estrogen, renin / aldosterone, cortisol, insulin
o Some ‘mechanically’ driven
* Designed to optimize conditions for fetus & prepare for delivery
o Delivery of oxygen & nutrients
Cardiovascular & Hematologic
* Vascular
o Decreased tone / vaso-relaxation
+ SVR decreased 20%
o Positional effects
o Placenta – low resistance shunt
* Hematologic
o Blood volume increases 50-100%
o RBC increases 25-40%
+ Relative anemia (“physiologic”)

Hematologic
* Hypercoagulable
o Estrogen & Vascular stasis
o Increased risk for thromboembolic disease
+ Increase in fibrinogen, all coag factors except II, V, XII
+ Fall in protein S and sensitivity to APC
* Fall in platelets and factor XI and XIII
* Increase in WBC

Changes in the Pump
* Cardiac axis displaced cephalad and left
o PMI lateral & elevated (not just due to baby!)
+ Altered thoracic dimensions
o Left axis deviation
* Murmurs > 96%
o Virtually all valves
+ Esp. Aortic and Pulmonary
+ Mammary Souffle
* Rate – increased (80’s typical)
* Ventricular distention – 25% increase
* Rhythm
o Non-specific ST & T changes
o Increase in dysrhythmias
+ Physiologic hypokalemia
* Anatomy
o LVH & Pericardial effusion
* Function
o Increased & markedly fluctuating output

Blood Pressure
Pregnancy Adaptations
Anatomical considerations
Uterine Position over Time
Cardiac Output – Positional Effects
* Aorto-caval Compression
Labor Changes
* SVR – Increased 10-25% with CTX
* Volume – autotransfusion 300-500cc
* Cardiac output -
o <3cm Increased 17%
o 4-7cm Increased 23%
o >8cm Increased 34%
The Fetus and Placenta
* Fetus (aka – “the parasite”)
o A sensitive survivor
o A window
* Placenta
o A veritable hormone factory
o Receives 20-25% of cardiac output*
+ 750-1000 ml/min
+ Refractory to vasoactive meds
o Uses as much O2 as fetus

Normal physiology or disease?
Signs & Symptoms of Normal Pregnancy that may Mimic Heart Disease
* Signs
o Peripheral edema
o JVD
* Symptoms
o Reduced exercise tolerance
o Dyspnea
* Auscultation
o S3 gallop
o Systolic ejection murmur
* Chest x-ray
o Change in heart position & size
o Increased vascular markings
* EKG
o Nonspecific ST-T wave changes
o Axis deviation
o LVH
Other systems
Changes in the Filter
* Renin – stimulated by progesterone
o Also made by placenta
o Angiotensinogen Angiotensin I Angiotensin II Aldosterone Distal tubule
+ Net absorption of Na+
+ Excretion of K+
+ Water retention: 6-8 liters
* Increased renal blood flow
o 50-75% increase
o GFR – 50% increase
o Decreased Albumin = lower colloid oncotic pressure

Other urinary tract changes
* Ureteral dilation / hydroureter
o Smooth muscle relaxation
o Later exacerbation by uterine obstruction
o Urinary stasis*
* Dilation of pelves and calyces
* Increased kidney size
Lungs and respiration
Respiratory Adaptations
o No change in rate or IRV
o Thorax
+ Tr. Diameter 2cm; circumference 5-7cm
o Increased minute ventilation
o Reduced FRC – 20%
o Increased Tidal Volume – 30-40%
o Compensated respiratory alkalosis
+ pH 7.4+
+ PaO2; PaCO2 (40 – 30)
+ Drives gradient b/w mom and fetus

Respiratory Changes
Gastrointestinal
* Slowed GI motility
o Constipation, early satiety
* Relaxation of LES
o GERD
* Nausea / vomiting
o Often proportional to HCG level
* Liver / gallbladder
o Biliary stasis, cholesterol saturation
+ More stones
o Coagulation factors
o Increased binding proteins (thyroid, steroid, vitamin D)
Other “Adaptations”

* “I can’t see my feet!!!”
o Altered center of gravity
o Altered gait
o Greater joint laxity
+ Widening of symphysis pubis
+ Affects other joints
+ Thorax; widened costovertebral angle
o Fatigue / somnolence

Integumentary Changes
* Spider angiomata and palmar erythema
* Hair growth (abdomen and face)
* Mucosal hyperemia
* Striae gravidarum
* Hyperpigmentation (esp. linea nigra)
o Rashes and acne relatively common
Other Endocrine
* Pancreas
o Carbohydrate metabolism -Insulin resistance
+ Human placental lactogen, cortisol
* Thyroid Function
o Increased TIBG (via liver)
o Increased total T4 and T3
+ free levels unchanged
+ HCG suppresses TSH
* Adrenal function
o Free plasma cortisol is elevated
+ CRH from placenta stimulates ACTH
Immunology

* Must adapt to accept ‘allograft’
* Immune response altered, but not deficient
* Modulates away from cell-mediated cytotoxic effects
o Progesterone effect
o NK cells decrease by 30%
o Enhanced humoral / innate immunity
+ Immunoglobulins still active
+ IgG crosses placenta
o More susceptible to CMV, HSV, Varicella, Malaria
o Decrease in symptoms of some autoimmune disorders

Pregnancy – not a disease

* Profound changes in physiology and anatomy
* Affects most organ systems
* Can dramatically impact disease states, susceptibility, and treatment
* Almost all will encounter and treat pregnant women
o Even if you don’t know it
* Under-appreciation of changes will lead to suboptimal treatment or outright mistakes

Physiologic Changes in Pregnancy.ppt

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Infectious Diseases of the Skin and Eyes

Infectious Diseases of the Skin and Eyes

Skin Structure

Natural Defenses of the Skin
* Keratin
* Skin sloughing
* Sebum: low pH, high lipid
* Sweat: low pH, high salt, and Lysozyme, which digests peptidoglycan

Normal Skin Flora
* Propionibacterium acnes
* Corynebacterium sp.
* Staphylococci
o Staphylococcus epidermidis
o Staphylococcus aureus
* Streptococci sp.
* Candida albicans (yeast)
* Many others

The Eye
* Normal flora sparse
* Similar to skin flora
* Tears have lysozyme, IgA

Bacterial eye infection resulting from injury is a medical emergency!

Bacterial Skin Infections
* Acne
* Necrotizing fasciitis
* Leprosy

Acne
* Propionibacterium acnes: Gram + rod
* Digests sebum
* Attracts neutrophils
* Neutrophil digestive enzymes cause lesions, “pus pockets”

Microscopy
Acne
* Most common skin disease in humans
* Oil-based cosmetics worsen disease
* No effects of diet

Acne Treatments
* Benzoyl peroxide dries plugged follicles, kills microbes
* Tetracycline (antibiotic)
* Accutane – inhibits sebum formation

Necrotizing Fasciitis “Flesh Eating Strep”
Streptococcus pyogenes (Group A Strep)
* Tissue digesting enzymes
o Hyaluronidase
o Streptokinase
o Streptolysins
* Rapidly spreading cellulitis may lead to loss of limb

Necrotizing Fasciitis
* Disease starts as localized infection
* Pain in area, flu-like symptoms
* Invasive and spreading
* May lead to toxic shock (drop in blood pressure)
* Incidence 1-20/100,000
* 30-70% mortality
* Surgical removal, antibiotics

Hansen’s Disease: Leprosy
Mycobacterium leprae
* Disease of skin and nerves
* Change of pigmentation, loss of sensation
* Slow progressing
* Transmits poorly
* Droplet or skin contact?

Hansen’s Disease: Leprosy
* Mycobacterium leprae
* Acid fast bacterium
* Slow growth
* Strict parasite
* Multiplies in macrophages
* Prefers cool areas of body
* Long course, drug cocktail


Virus Infections of the Skin: Rashes
Maculo-papular rashes
(flat to slightly raised colored bump)
Measles virus (Rubeola)
Rubella virus (German Measles)
Roseola (Human Herpesvirus-6)
Fifth Disease (Human Parvovirus B19)

Measles
* Viral infection through aerosol droplet: One of the MOST communicable viruses
* Initial infection of the oro-pharynx

 local infection lymph node(s) (of the neck)
 lymphocyte associated viremia
Fever, malaise
 Spread throughout the body
 Shed in respiratory tract secretions
Koplik’s spots
Skin Rash
 Recovery; life long immunity

* Effective childhood vaccine (2-3 doses): MMR (measles, mumps, rubella), but disease still exists worldwide

An example of the rash of measles.
Note flat, reddened areas

Measles World Wide
* Measles is the leading cause of vaccine-preventable death among children
* Millions of children still remain at risk from measles.
* In developed, measles death rates range from 1-5%, but among malnourished children, the death rate reaches 10-30%
* Over 500,000 children under the age of five die each year.
* Measles causes health complications, including pneumonia, diarrhea, encephalitis, and corneal scarring.
* The primary reason for ongoing high childhood deaths is the failure to deliver at least one dose of measles vaccine to all infants.

The Measles Vaccine Initiative 2001
American Red Cross
United Nations Foundation (UN Foundation)
United States Centers for Disease Control and Prevention (CDC)
World Health Organization (WHO)
United Nations Children's Fund (UNICEF)

Measles World Wide

Rubella
* Viral infection through aerosol droplet; systemic infection
* A ~Mild~ rash
* Serious for a fetus when contracted in the first trimester of pregnancy
* Disrupts fetus development of the CNS and/or other organs: Congenital Rubella Syndrome
+ Small birth weight, blindness, hearing loss, mental retardation, heart problems
+ Infection lasts for months-years in the newborn
* Vaccine highly effective (MMR)

Features for Measles and Rubella
Virus Infections of the Skin: Vesicles
Vesicular or pustular rash
(elevated lesions filled with fluid)
Smallpox (Human Pox virus)
Cold Sores (Human simplex 1 and 2)
Chickenpox (Human Herpesvirus-3)

Chickenpox “Varicella – Zoster”
* Common virus; decreasing disease in the USA due to effective childhood vaccine
* Benign disease with life long immunity
* Life-threatening for immunocompromised individuals
* Recuperation can result in life long benign Varicella-zoster virus latency
* May re-emerge as shingles (skin lesion): Should we vaccinate adults?

Chickenpox virus in the body
* Viral infection through aerosol droplet; systemic infection

 local infection in lymph node(s) (of the neck)
 lymphocyte associated viremia
Fever, malaise
 Spread throughout the body
 Shed in respiratory tract secretions and
Skin Vesicles (small blisters of clear fluid)
 Recovery with virus latency in neurons
 Life long immunity
* May re-emerge as shingles and spread to others (skin vesicular lesions):






Chicken pox reemerges as Shingles
Causes: stress, X-ray treatments, drug therapy, or a developing malignancy, or ?
Varicella-zoster virus reemergence as shingles

Smallpox
* A disease with an interesting history
* Very infectious viral disease (epidemic)
* The disease has been eliminated due to world-wide vaccine program:
+ Vaccinia: a Jennerian vaccine

Named for Edward Jenner, 1796
* The virus has been preserved in government labs by agreement, at CDC in Atlanta, and in Russia
* Considered a bioterrorism agent

Features of Chickenpox and Smallpox.

Virus Infections of the Eye
Herpesvirus Keratitis (Human simplex 1)
Chlamydial infection of the eye
Chlamydia trachomatis causes trachoma
and can lead to blindness

Warts and Papillomas
* Mostly a benign viral infection
* Nearly everyone is infected!
* Contact transmission; fomite transmission
* Different virus types
o Plantar warts (HPV-1)
o Flat warts (HPV-3,10,28,49)
o Genital Warts (HPV 6,16,18,31)

Common warts
Infectious Diseases of the Skin and Eyes.ppt

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Drugs for Viral Infections

Drugs for Viral Infections

Virus vs. Bacteria

* Compare and contrast structural components of bacteria and viruses
* Describe a viron.
* Identify indications for viral infection pharmacotherapy.

Challenges of Anti-Viral Therapy
* Rapid mutation
* Intracellular nature of virus
* Drugs have narrow spectrum of activity

HIV vs. AIDS
* Discuss the difference between a virus and a retrovirus.
* Differentiate between HIV infection and AIDS.
* Describe the replication of HIV.

Pharmacotherpy for HIV-AIDS
* Identify the therapeutic goals of therapy.
* Classifications:
o Nucleoside reverse transcriptase inhibitors (NRTI)
o Nonnucleoside reverse transcriptase inhibitors (NNRTI)
o Protease Inhibitors
o Neucleotide reverse transcriptase inhibitor (NtRTI)
o Fusion (entry) inhibitor

HIV-AIDS Pharmacotherapy
* Compare and contrast the mechanism of action of:
o Reverse transcriptase inhibitors
o Protease inhibitors
o Fusion inhibitors
* Identify reasons treatment failures occur.

Antiretrovirals: NCs
* Drug is not a cure
* Prior to RX: assess for sx of HIV, opportunistic infection, use of herbals
* Monitor viral load
* Verify ordered combination drugs
* Common side effects:
o Fatigue, headache, GI disturbances
* Other side effects dependent upon specific drug

Antiretrovirals: NCs

* Most contraindicated: pregnancy, lactation
* Side effects can influence ADLs
* NRTIs: cautiously: pancreatitis, PVD, neuropathy, kidney or liver disorders, cardiac disease, alcohol abuse
* NNRTIs: judiciously use in liver impairment, CNS disease
* PIs: potential risks if sensitive to sulfonamides, liver disorders, renal insufficiency

Antiretrovirals: NCs

* Variations in administration instructions:
o NRTIs: empty stomach, water only, no fruit juice
o Nevirapine (Viramune) and saquinavir (Invirase) – take with food to decrease GI upset
o Contact HCP before taking any OTC med or supplement

Antiretrovirals: Client Teaching

* NRTIs: report fever, skin rash, abd pain, n/v, numbness or burning of hands/feet
* NNRTIs: report fever, chills, rash, blistering or reddening of the skin, muscle or joint pain
* PIs: report rash, abd pain, headache, insomnia, fever, constipation, cough, fainting, visual changes

Antiretrovirals: Client Teaching

* Wash hands frequently; avoid crowds
* Increase fluid intake; empty bladder frequently
* Abstinence or barrier contraception
* Do not share needles
* Take medications as ordered
* Sufficient rest and sleep; healthy diet
* Keep all scheduled appts and lab visits

Perinatal HIV Transmission
Discuss pharmacotherapy for the prevention of perinatal transmission.

Occupation Exposure
* Identify risk factors for occupational exposure to HIV.
* Describe post HIV exposure prophylaxis.

Herpesvirus Infections
* HSV-1
* HSV-2
* CMV
* VZV
* EBV
* Herpesvirus 6
o Children: roseola
o Immunocompromised: hepatitis or encephalitis

Herpesvirus Infections
* Triggering events:
o Immunosuppression
o Physical challenges
o Emotional stress

* Pharmacologic goals:
o Relieve acute symptoms
o Prevent recurrences

Antivirals: NCs
* Baseline: VS, wt, CBC, viral cultures, LFTs, RFTs
* Cautiously: pre-exisiting renal or liver dysfunction
* Judiciously: pregnancy
* Routes: IV, oral, topical, inhalation
o instruct re: proper technique
o Emphasize compliance

Antivirals: NCs
* Generally well tolerated:
o Take with food if GI upset
* Severe adverse reactions:
o Renal Failure, Thrombocytopenia
* More frequently side effects:
o Headache
o Fatigue
o Dizziness

Antivirals: Client Teaching

* Meds do not prevent transmission
o avoid activities that may transmit
* Immediately report: hematuria, bruising, jaundice, fever, chills, confusion, nervousness, dizziness, nausea, vomiting
* Complete full course of treatment
* Keep scheduled appts and lab visits

Antivirals: Client Teaching

* Caution while performing hazardous activities
* No other prescription, OTC, herbals or supplements without HCP approval
* Apply topicals with applicator or glove
* No other creams, ointments, or lotions to infected sites

Influenza

* Describe the characteristics of influenza.
* Differentiate between primary and secondary pharmacotherapy for influenza infections.
* Differentiate between antiviral and neuroaminidase inhibitor therapy.

Viral Hepatitis
* Caused by several different viruses with unique clinical features
* All cause inflammation and necrosis of liver cells
* Acute
o Fever, chills, fatigue, anorexia, nausea, vomiting
* Chronic
o Prolonged fatigue, jaundice, liver cirrhosis, hepatic failure

Viral Hepatitis

* Differentiate between Hepatitis A, Hepatitis B, and Hepatitis C.
* Compare and contrast pharmacotherapy for Hepatitis A, Hepatitis B, and Hepatitis C.

Viral Hepatitis Exposure
Compare and contrast post-exposure prophylaxis for Hepatitis A, Hepatitis B, and Hepatitis C.

Drugs for Viral Infections.ppt

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