Pathology Flashcards
What are 4 pathological states leading to urinary tension?
What is a pathological state leading to urinary incontinene?
Tension
- Anticholinergic medications (ex. atropine, gravol, ipatropium)
- Spinal cord injury
- Diabetics
- Stroke damaging the pontine micturition center
Incontinence
- Stroke damaging the pontine storage center
Define the following:
Urinary Tract Infection
Urethritis
Cystitis
Acending pyelonephritis
Pyelonephritis
Asymptomatic Bacteriuria
UTI = an infection affecting part of the urinary tract
Cystisis = an infection of the bladder
Ascending pyelonephritis = UTI affecting the ureters on the way up to the kidneys
Pyelonephritis = an infection of the kidneys
Asymptomatic Bacteriuria = presence of bacteria in urinary tract in the absence of symptoms
What makes a UTI “complicated” (4)
- Presence of DM
- Pregnancy
- Male
- Immunocompromised
Epidemiology of UTI
- How many million people have a UTI each year globally?
- What % of women have a UTI in a given year?
- What % of women have a UTI over their lifetime
- Sexual activity causes what % of bladder infections in young sexually active women?
- What is the age range with the most frequent UTIs?
- 150 million
- 10%
- 50%
- 75-90%
- 16-35
Why do women have an increased risk of a UTI than men? Why does this risk increase with age?
The shorter urethra makes it more likely for a pathogen to invade.
Post-menopausal loss of estrogen leads to the loss of protective vaginal flora
- What bacteria is the most common cuase of a community-acquired UTI? Second most common?
- What 2 bacteria are more likely to be the culprit of a blood-borne UTI?
- What are 2 types of bacteria that can cause urethritis but not cystitis?
- E. Coli, Staphylococcus Saprophyticus
- Staphylococcus Aureus, Salmonella
- Chlamydia trachomatis, Mycoplasma genitalium
What are the gram negative bacteria that can cause a UTI? Gram positive?
What factors increase your risk of developing a UTI? (11)
- Urinary catheter (Foley)
- Sexual intercourse
- Divers using condom catheters or external catching devices
- Female gender
- Diabetes (inhibition of neutrophils)
- Obesity
- Family history
- Lack of circumcision
- Impaired bladder emptying
- Distortion of veiscoureteral junction either from a past infection or a congenital malformation
- Chronic prostatitis
What 5 organisms are associated with a UTI in the context of a catheter?
- E. Coli
- Klebsiella
- Pseudomonas
- Candida albicans
- Enterococcus
What is a vesicoureteral reflux?
The backflow of urine from the bladder and up the ureters
What is the pathogenesis of a UTI?
- Bacteria enter the urethra (usually from the bowel) and travels to the bladder or gains access to the tract via blood or lymph
- Once in the bladder, they create a biofilm by attaching their pili to toll-like receptors. This increases their reistance to our immune system
- Neutrophils attempt to clear the pathogen
What are symptoms of a lower UTI?
- Burning (pain) with urination
- Increased frequeny and urgency of urination
- Difficulty urinating
- Feeling the need to urinate in the absene of a full bladder
- Suprapubic and lower back pain
(6. Blood/pus in urine –> rare)
What are the symptoms of a kidney infection?
- Fever with a high spiking pattern and termination after 3 days of treatment
- Nausea and vomiting
- Flank pain and pain at the costovertebral angle
- Lower UTI symptoms
(5. Blood/pus in the urine –> rare)
What are indications of a UTI in children? Elderly?
Children = fever, poor feeding, vomiting, poor sleeping, fussy, jaundice, new onset urinary incontinence or regression in potty training
Eldelry = delirium, fatigue, fever, chills, and incontinence
What are 6 possible investigations for a UTI?
- Urinalysis = leukocyte esterase and nitrites, (white blood cell casts indicate pyelo)
- Urinalysis with microscopy = >2(m)-10(f) wbc/HPF, rbc
- Urine culture = 100,000 CFU/mL
- Renal U/S = hydro-nephrosis, malformations
- Voiding cystourethrogram = injection of dye with real-time X-ray during urination
- Renal scintigraphy with DMSA = kidney scarring
When is it indicated to do a urinary culture when you are suspicious of a UTI? (5)
- Pregnant females
- All females under 2 years of age
- Uncircumcised males under 1 year of age (but really all males)
- Those presenting with recurrent UTIs
- Elderly with signs of systemic infection and advanced dementia preventing communication
What are complications that can arise from a UTI? (7)
- If during pregnancy, pyelonephritis is more likely to occur
- If during pregnancy, risk of low birth weight or premature infant
- Permanent kidney damage
- Renal papillary necrosis if a kidney infection
- Urethral narrowing in men
- Bacteremia
- Sepsis
What are 5 things you can give to someone with a UTI?
What are 3 types of preventative measures for a UTI?
Treatment:
- Antibiotics
- Methenamine
- Phenazopyridine
- Acetaminophen
- Topical vaginal estrogen
Prevention:
- Drinking lots of fluids
- Good hygiene (wiping from urethra to rectum in women)
- Urinate right after sexual intercourse
How do you treat asymptomatic bacteriuria?
Only treat if pregnant or after a urological procedure.
- Get urine culture
- Treat with amoxicillin or nitrofurantoin
How do you treat cystitis?
Uncomplicated = short course of antibiotics
Complicated = long term of IV antibiotics
How do you treat pyelonephritis?
Antibiotics
How do you treat a perinephric abscess?
- IV antibiotics
- Incision and drainage of the abscess
What are some examples of gram-negative bacteria? What are some examples of gram-positive bacteria? How can you tell which bacteria type has caused a UTI?
Gram negative:
= E. Coli, Klebsiella, proteus, enterobacter, citrobacter, salmonella
Gram positive:
= Enterococcus, staphylococcus saprophyticus, staphylococcus aureus
Gram negative bacteria produce nitrites
What is Pasternacki’s sign?
Pain at the costovertebral angle
What is prostatitis?
What is chronic pelvic pain syndrome?
Acute or chronic infectious and non-infectious abnormalities of the prostate gland leading to enlargement.
When non-infectious, they are referred to as chronic pelvic pain syndrome.
What causes infectious prostatitis? (broadly speaking)
Bacteria
What is the presentation of prostatitis? (acute vs. chronic)
Acute:
- Dysuria
- Increased frequency/urgency of urinating
- Pain in the prostatic pelvic or perineal area
- Fever and chills
- Symptoms of bladder outlet obstruction
Chronic:
- Recurrent episodes of cystitis
- Pain in the prostatic pelvic or perineal area
Other:
- Cloudly/bloody urine
- Abdominal pain
- Pain in penis or testicles
- Painful ejaculation
What is the nephrotic syndrome?
What is the difference between primary and secondary nephrotic syndrome?
What is the nephrotic tetrad seen in this syndrome?
Syndrome = proteinuria, hypoalbuminemia, peripheral edema
Primary = idiopathic, secondary = caused by something we know
Tetrad = the above 3 + hypercholesterolemia
Are adults or children more affected by nephrotic syndrome? Men or women?
What is the most common disease causing nephrotic syndrome in children? adults?
Adults, men
Children = 70-90% from minimal change disease
Adults = 30-40% from membranous glomerulonephritis
What is glomerulonephritis?
Acute inflammation of the kidney, typically due to an immune response
What is minimal change disease? Describe the pathogenesis.
A type of nephrotic syndrome characterized by podocyte effacement and caused by a T-cell mediated process
The loss of negative podocytes allows albumin to move into the Bowman’s capsule
What is membranous glomerulonephritis? Describe the pathogenesis.
What are some secondary causes of it?
A type of nephrotic syndrome characterized by inflammation and spike-like thickening of the glomerular basement membrane.
Subepithalial deposits (antigen-antibody complexes) activate the complement system which creates a membrane attack complex. This complex damages podocytes and mesangial cells and recruits other inflammatory cells. All together, the GBM is damaged and leaky to proteins.
Secondary = infection, malignancy, autoimmune condition, medications
What is focal segmental glomerulosclerosis? Describe the pathogenesis.
What are some secondary causes of it?
A type of nephrotic syndrome characterized by sclerosis affecting only parts of only some glomeruli.
Podocyte damage (idiopathic) allows proteins and lipids to pass by. Some get trapped in the space around the capillaries causing hyalinosis. Over time the trapped molecules develop into sclerosis.
Secondary = sickle cell disease, HIV-nephropathy, heroin-nephropathy, kidney hyperperfusion, increased glomerular capillary pressure
What are 6 outcomes of mass proteinuria and how do they occur?
- Low albumin = loss into urine
- Hypercholesterolemia = liver over-active to replace albumin
- Edema = decreased plasma oncotic pressure from low albumin so that water moves into interstitium
Edema –> decreased CO –> decreased renal blood flow –> decreased GFR –> RAAS –> increased water re-absorption –> worsening edema
- Hypovolemia = decreased plasma oncotic pressure from low albumin so that fluid moves into interstitium
- Increased risk of infection = loss of antibodies into urine
- Hypercoagulable state = greater loss of antithrombin than clotting factors
How does nephrotic syndrome present? (11)
Proteinuria
- Frothy urine
Hypercholesterolemia
- Xanthelasma
- Xanthomata
Hypoalbuminemia
- Tiredness
- Cachexia
- Leukonychia
Peripheral edema
- Periorbital swelling
- Ascites
- Pitting
- Breathlessness (pulmonary edema, pleural effusion)
- Arthralgia
What are diagnostic findings in nephrotic syndrome for:
- Urinalysis
- Blood analysis
- Chest X-ray
- Renal U/S
- elevated (>3.5 g/day) protein, urine Ig, urinary casts
- Low (<2.5g/dL) albumin, high urine protein/creatinine, high cholesterol (LDL/VLDL), LFT showing heightened liver function, possibly low Ca++, possibly high CRP, possibly high glucose (fasting/HbA1)
- Possibly pleural effusion and/or pulmonary edema
- Possibly damage/congenital abnormality?
Fill out the following chart for nephrotic syndrome renal biopsy:
What are possible complications of nephrotic syndrome? (10)
- Thromboembolic disorder from decreased antithrombin
- Infection from lost immunoglobulins (peritonitis > lung > skin > UTI > miningoencephalitis > sepsis)
- Acute kidney failure from hypovolemia
- Pulmonary edema
- Hypothyroidism from lost thyroxine
- Vitamin D deficiency and resulting hypocalcemia
- Microcytic hypochromic anemia from lost iron
- Protein malnutrition and wasting
- Growth retardation from lost hormones
- Cushing’s syndrome from the body trying to compensate with the RAAS
Nephrotic syndrome treatment:
- What is the first line treatment for minimal change disease in children?
- What is another option for treatment (especially frequent relapsers)
- Should steroids be used to treat membranous glomerulonephritis? Focal segmental glomerulosclerosis?
- Steroids (8 week course)
- Alkylating agent (ex. cyclophosphamide)
- Yes but treat underlying disease; Unsure –> inconsistent results
How do you treat the different components/complications in nephrotic syndrome?
What is pre-renal acute kidney injury refer to?
Kidney injury due to decreased blood flow into the kidneys
What are causes of pre-renal acute kidney injury?
- Absolute fluid loss (hemorrhage, vomiting, diarrhea, burns, low intake)
- Relative loss of fluid (distributive shock, CHF)
- Renal artery problems (stenosis, embolus)
- Medications (ACEi, NSAIDs)
- Hypotension
What happens in pre-renal AKI?-
Less blood gets to the kidnesy and the GFR drops. This causes:
- High levels of nitrogen in the blood (azotemia)
- Low urine excretion (oliguria)
- RAAS activation and resultant increase in BP
- Urea reabsorption
Fill in the following lab findings for pre-renal AKI:
How do you treat pre-renal AKI?
- Determine if they are volume high or low
- If high give diuretics; if low give IVF
- Correct the underlying cause
What are 4 main reasons for administering diuretics?
What are 8 other reasons?
- Decrease expanded EC volume (edema)
- Decrease blood pressure
- Increase urinary excretion of excess ions
- Prevent anuria in acute renal failure
Dialysis disequilibrium syndrome, calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus, epilepsy, metabolic alkalosis, altitude sickness, cystic fibrosis
What is hypertension a risk for? (5)
- CAD
- Stroke
- Heart failure
- Renal disease
- Peripheral vascular disease
What is the difference between essential and secondary hypertension?
How do you differentiate between them?
Essential = cause of the BP elevation is unknown (90% of cases)
Secondary = known problem is causing elevated BP
What are the indications for:
- Pre-hypertension
- Hypertension stage I
- Hypertension stage II
- Hypertensive urgency
- Hypertensive emergency
- SBP > 120; DBP > 80
- SBP > 135; DBP > 85
- SBP > 140; DBP > 90
- BP > 180-220/120 with no signs of end organ damage
- BP > 180-220/120 with signs of end organ damage
What are 5 non-modifiable and 9 modifiable risk factors for high blood pressure?
Non-modifiable:
- Family history positive
- Older age
- Male gender
- African American race
- Chronic kidney disease
Modifiable:
- Lack of physical activity
- Unhealthy diet (high in sodium)
- Overweight/obese (strain on CV system)
- Excess alcohol intake
- Sleep apnea
- High cholesterol
- Diabetes
- Smoking/tobacco
- Stress
What things are considered to be “end-organ damage”? (6)
- CHF
- LVH
- Aortic dissection
- Kidney failure
- Pulmonary edema
- Retinal hemorrhage
What are 3 possible causes of primary hypertension?
- Genetics (complex polygenic disorder, RAAS genes)
- Defects in regulation (SNS+, abnormal vascular tone regulators, abnormal ion channels, inappropriate hormone regulation, problems with sensors, abnormal CNS control)
- Insulin resistance and obesity (angiotensinogen released from adipocytes, increased viscosity, insulin activating SNS)
What is part of your work-up in investigating possible causes of secondary hypertension?
- General screening
- Urinalysis and serum creatinine
- Electrolytes (low K+)
- Blood analysis (BUN, glucose, cholesterol, triglycerides)
- Hormone levels (24 hour urine cortisol, TH, PTH, 24 hour urine metanephrines, GH)
- Sleep study
- Bood pressure differences from R to L arm and arm to leg
What are 4 big categories for possible causes of secondary hypertension?
- Exogenous (medications)
- Renal cause (damage, RAAS)
- Mechanical cause
- Endocrine cause
What are 8 possible exogenous causes of secondary hypertension and how do they increase BP?
- Oral contraceptives = estrogen increases angiotensinogen synthesis
- Glucocorticoids = increased SNS
- Cyclosporine
- Erythropoietin = increased blood viscosity
- Sympathomimetic drugs = increased SNS
- NSAIDs = augmentation of renal sodium/water retention
- Ethanol = increased SNS
- Cocaine = increased SNS
- Tyrosine kinase inhibitors
What are 2 major renal causes of secondary hypertension? How do they lead to high blood pressure?
How would you investigate?
- Renal parenchymal disease = damaged nephrons can’t excrete sodium and water –> increased BV –> increased BP
Investigations = low Na+ in urine and high Na+ in serum; possible proteinuria
- Renal arterial stenosis = blocking renal flow and causing RAAS activation
Investigations = abdominal bruit, hypokalemia, elevated aldosterone, imaging
What are 2 mechanical causes of secondary hypertension? How do they lead to high blood pressure?
How would you investigate?
- Coarctation of the aorta = decreased renal flow –> RAAS activation (possibly blunted baroreceptor response to increased BP)
Investigations = BP differences, claudication, fatigue, weak/absent femoral pulse, mid-systolic murmur, imaging
- Obstructive sleep apnea –> fatigue and glucocorticoid release or hypoventilation and hypercapnia
Investigations = sleep study
What are 7 endocrine causes of secondary hypertension?
- Pheochromocytoma
- Primary aldosteronism (ex. Conn Syndrome, bilateral hyperplasia)
- Secondary aldosteronism (ex. renin-secreting tumor, chronic liver disease)
- Glucocorticoid-remediable aldosteronism
- Cushing syndrome
- Thyroid abnormalities
- Acromegaly
Explain how the following endocrine causes lead to secondary hypertension. How would you investigate? How would you treat?
What are possible symptoms of progressive hypertension? (6)
- Sweating
- Headache
- Dizziness
- Epistaxis
- Flushing
- Blurred vision
*Usually asymptomatic until an event or routine exam
What are the complications of hypertension?
What is the pathogenesis of kidney injury as a result of hypertension?
- Vessel walls become thickened with hyaline infiltrate
- Increased hypertension induces smooth muscle hypertrophy and necrosis of capillary walls (fibrinoid necrosis)
- This reduces the vascular supply to the kidney
- Ischemic atrophy of the tubules and glomeruli then occur
What is hypertensive encephalopathy?
Increased intracranial pressure from elevated BP resulting in headache, blurred vision, confusion, somnolence, and coma
What is accelerated-malignant hypertension?
Hypertension resulting in acute damage to retinal vessels and presenting with hemorrhage, exudate, and sometimes papilledema on fundoscopy
What are some non-pharmacologic treatments for hypertension?
- Weight reduction
- Exercise
- Diet (High K+, Ca++, Mg++; low caffeine, salt, alcohol)
- Smoking cessation
- Relaxation therapy
What are 4 classes of drugs used in treating hypertension?
- Diuretics
- Sympatholytics
- Vasodilators
- RAAS blockade
How do diuretics improve hypertension?
What type of hypertensive patient would be given a diuretic?
Thiazides and potassium sparing diuretics promote Na+ excretion and thus water excretion
(Loop diuretics are too potent and short-lived)
Patient = mild to moderate hypertension; normal renal function; salt sensitive people
How do sympatholytics improve hypertension?
What type of hypertensive patient would be given a sympatholytic?
Beta blockers reduce HR and contractility and thus CO which decreases renin
Central alpha-adrenergic agonists reduce SNS signaling to heart, vasculature, and kidney
Systemic alpha-adrenergic blockers relax vascular smooth muscle
Patient = older men shoulduse systemic alpha blockers
How do vasodilators improve hypertension?
Calcium channel blockers reduce cardiac heart contraction and vascular smooth muscle contraction
Hydralizine and minoxidil directly relax vascular smooth muscle of precapillaries
How do RAAS blockade drugs improve hypertension?
What type of hypertensive patient would be given a RAAS blockade?
ACE inhibitors block angiotensin II production which reduces systemic vasoconstriction and water retention
Angiotensin II receptor blockers reduces systemic vasoconstriction and water retention
Direct renin inhibitors reduce systemic vasoconstriction and water retention
Patient = slows down renal failure in diabetic nephropthy
What is renal artery stenosis?
The narrowing of one or both of the renal arteries
What are the 2 most common causes of renal artery stenosis?
- Atherosclerotic renal artery disease (~90%)
Fat, calcium, and immune cells form a crusty rim around inside of artery, usually at beginning
- Renal Fibromuscular Dysplasia (~10%)
Fibrous collagen, connective tissue, and smooth muscle develop abnormally causing a series of bluges, usually at middl to distal end
What are some uncommon but possible causes of renal artery stenosis? (6)
- Vasculitis
- Neurofibromatosis
- Congenital bands
- Extrinsic compression
- Radiation
- Embolus
What is the pathophysiology of renal artery stenosis?
- Narrowing of renal afferent decreases renal blood flow
- JG cells release renin –> RAAS
- RAAS causes systemic and renal constriction
- This maintains GFR at first, but continual constriction leads to systemic hypertension
- Complications such as stroke and heart attack can then occur
What are some complications of renal artery stenosis?
- Renal ischemia –> renal atrophy –> fibrosis
- Stroke from systemic hypertension
- Heart attack from systemic hypertension
What are the signs and symptoms of renal artery stenosis?
Usualy asymptomatic
May have a headache and blurry vision from hypertension
May have flash pulmonary edema brought on by a palliating factor
How do you diagnose renal artery stenosis?
- Renal bruits
- Urinalysis (high serum creatinine, hypokalemia, protein hyaline, casts)
- Imaging (atrophy, malformations)
- Renal arteriography (visualize arteries for the blockage)
- Captopril challenge test (high renin baseline, decreased renin clearance in response to captropril, an ACE inhibitor)
What is the treatment for renal artery stenosis?
- Medications aimed at managing hypertension (diuretics, ACEi, ARBs, vasopressors, sympatholytics)
- Be careful using a RAAS blockade (25-30% rise in creatinine is ok) - Healthy eating and exercise
- Surgery (balloon angioplasty +/- stent, bypass, removal)
- Atherosclerotic medications (aspirin, statins)
What is metabolic acidosis? What are two different types?
MA = a decrease in serum HCO3- causing pH to lower to <7.35
High anionic gap = decreased pH caused by excess H+ that isn’t part of the anion gap
Non-anionic gap = decreased pH due to loss of HCO3- (offset by increased Cl-)
What are causes of high anionic gap metabolic acidosis? (13)
MUDPILES CT / GOLDMARK
- Glycols (ethylene, poly, propylene)
- 5-Oxoproline (chronic acetaminophen ingestion)
- Lactate
- D-lactate (short gut syndrome)
- Methanol
- Aspirin (salicylates)
- Renal failure
- Ketoacidosis
- Uremia (sulphates, phosphates)
- Paraldehyde
- Carbon monoxide
- Cyanide
- Toluene
- Massive rhabdomyolysis
What are causes of non anionic gap metabolic acidosis? (10)
USED CRAP
- Ureterosigmoidostomy
- Small bowel issues
- Extra chloride administration
- Diarrhea
- Carbonic anhydrase inhibitors
- Renal tubular acidosis
- Addison’s disease (hyperkalemia)
- Pancreatic issues
- Parenteral nutrition
- Paraprotein states
How do you determine whether a non-anionic gap metabolic acidosis has a renal etiology or non-renal etiology?
Renal = positive urine anionic gap
Non-renal = negative urine anionic gap
How does the body compensate in metabolic acidosis and what is the result of these compensations? (3)
- Increased absorption of H_ into renal cells –> hyperkalemia
- Increased respiratory rate and depth –> increased minute ventilation, decreased CO2
- Renal compensation –> decreased Na+ and water uptake
What are signs/symptoms of metabolic acidosis? (7)
- Headache
- Altered mental status
- Decreased visual acuity
- Chest pain/palpitations
- Kussmaul respiration
- Nausea/vomiting, abdominal pain, altered appetite, weight gain
- Muscle weakness, bone pain, joint pain
What are serious neurological complications of metabolic acidosis? Cardiac complications?
Neural = coma, seizures
Cardiac = ventricular tachyardia, hypotension
How do you treat a metabolic acidosis?
- IV bicarbonate (50-100 mmol at time –> be careful of ABG readings)
- Dialysis if necessary (kidney failure or OD)
- Treat the underlying cause
What is metabolic alkalosis? What are two different types?
Metabolic alkalosis = an increase in serum HCO3- causing pH to increase to > 7.45
Chloride-responsive MA = chloride lost along with H+ (urine Cl- <10 mEq/L)
Chloride-resistant MA = chloride retained; retention of HCO3- primarily responsible (urine Cl- > 20 mEq/L)
What are causes of chloride-responsive metabolic alkalosis? (6)
- Diarrhea
- Vomiting
- Contraction alklaosis
- Post-hypercapnia
- Cystic Fibrosis
- Excess ingestion of antacids
What are causes of chloride-resistant metabolic alkalosis? (2)
- Hypokalemia
- Excess aldosterone (adrenal tumor, pheochromocytoma, congenital adrenal hyperplasia, Cushing’s)
How does the body compensate in metabolic alkalosis and what is the result of these compensations? (3)
- Increased secretion of H+ from cells –> hypokalemia
- Decreased respiratory rate and depth –> decreased minute venitlation and increased CO2
- Renal compensation –> retention of H+
Possible water gain; possible water loss
What ion is used to assess volume status in metabolic alkalosis?
Chloride
Fill in the fllowing chart for signs and symptoms accompanying the pathophysiological processes in metabolic alkalosis:
What are 4 serious complications of metabolic alkalosis?
- Neurological –> tetany/seizures/decreased mental status
- Decreased coronary blood flow –> arrhythmias
- Hypoventilation –> hypoxemia
- Increased ammonia production –> hepatic encephalopathy
How do you treat metabolic alkalosis? (6)
- Correct the cause
- Correct the deficiency (Cl-, water, K+, etc.)
- Expand ECF volume with normal saline if appropriate
- RAAS blockade
- O2 if necessary
(6. Rarely –> HCl infusion, aetazolamide, oral lysine HCl)
What is respiratory acidosis? What is the differene between acute and chronic?
A failure of the respiratory system leading to a blood pH <7.35
Acute = PaCO2 > 45 with acidemia
Chronic = PaCO2 > 45 with near normal pH and serum HCO3- >30 (renal compensation)
What are causes of acute respiratory acidosis?
Brainstem = stroke, meds/drugs
Neuromuscular = myasthenia gravis, trauma, ALS, G-B syndrome, muscular dystrophy
Airway obstruction = foreign object, asthma
Impaired gas exchange at alveoli:capillary = COPD, pneumonia, pulmonary edema
What are causes of chronic respiratory acidosis? (4)
COPD
Pickwickian syndrome
Interstitial Lung Disease
Thoracic deformities
How does the body compensate for respiratory acidosis? (3)
- Respiratory centers respond to baroreceptors and increase rate and depth of breathing
- Cellular buffering causes a 1 mEq/L HCO3- increase for every 10mmHg increase in PaCO2
3 Renal compensation causes a 3.5 mEq/L HCO3- increase for every 10mmHg increase in PaCO2 (increased bicarb reabsorption and production, renal excretion of carbonic acid)
What are some signs and symptoms of a respiratory acidosis?
- Headache
- Anxiety
- Blurred vision
- Restlessness
- Confusion
How is acute respiratory acidosis treated?
How is chronic respiratory acidosis treated?
Acute = address underlying cause and use artificial ventilation if needed
Chronic = manage underlying condition, give antibiotics/diuretics/bronchodilators/corticosteroids as needed, artificial ventilation if needed
What is respiratory alkalosis? What is the difference between acute and chronic?
Failure of the respiratory system leading to a blood pH of >7.45
Acute = low CO2 and high pH
Chronic = low CO2 and normal pH (renal compensation)
What are some causes for respiratory alkalosis? (9)
Respiratory center
- Normal response to hypoxia (pneumonia, PE, high altitude)
- Abnormal response to hypoxia (panic attack, OD on ASA)
- Brainstem disorders irritating center (tumor)
Iatrogenic increased respiration
- Wrong settings on a mechanical ventilator
Other causes
- Heart disorder
- Thermal insult
- Fever
- Compensation for volume loss in vocal cord paralysis
- Liver disease
How does the body compensate for respiratory alkalosis?
- Respiratory center senses low CO2 levels and responds by slowing down minute ventilation
- Cellular buffering causes 2 mEq/L HCO3- decrease for every 10 mmHg decrease in PaCO2 (proteins in cells excrete H+ into blood –> ex. Hb)
- Renal compensation causes 4-5 mEq/L HCO3- decrease for every 10 mmHg decrase in PaCO2 (release of more HCO3- into blood at the PCT)
What are some signs and symptoms of respiratory alkalosis?
- Dizziness/light-headedness
- Bloating
- Numbness and muscle spasms in hands and feet
- Arm tingling
- Chest discomfort, heart palpitations
- Confusion
- Dry mouth
- SOB
How is respiratory alkalosis treated?
- Treat the underlying cause
- ABG monitoring
- Paper bag breathing
- Pursed lip breathing
What [K+] is considered hyperkalemia? Hypokalemia?
Hyperkalemia = [K+] > 5.5 mmol/L
Hypokalemia = [K+] < 3.5 mmol/L
What are characteristics of an ECG in:
- Hyperkalemia?
- Hypokalemia
Hyperkalemia = peak T waves –> widening QRS complex –> absence o P waves –> sine waves –> asystole, ventricular fibrillation
Hypokalemia = T and U wave (biphasic T), prolonged QT interval, tachycardia
What are 3 complications of hyperkalemia?
What are 7 complications of hypokalemia?
Hyperkalemia:
- Arrhythmias
- Muscle weakness/spasms
- Paralysis
Hypokalemia:
- Arrhythmias
- Weakness/fatigue
- Muscle cramps
- Paralysis
- Rhabdomyolysis
- Polyuria from ADH inhibition
- Interstitial fibrosis
How do you treat hypokalemia?
- Replace potassium (KCl- a good cohice; KHCO3- good if there is acidosis, do NOT give glucose, ensure there is enough Mg)
- Give calcium to eliminate arrhythmias
- Treat the underlying cause
How do you treat hyperkalemia?
- Remove the excess K+
- Renal = Non-K+ sparing diuretic
- GI = resins (binds K+) or induction of diarrhea
- Shift (glucose, beta agonist, bicarbonate)
- Dialysis in extreme cases - Give calcium to eliminate arrhythmias
- Treat the underlying cause
What is shock from a medical standpoint?
A life threatening condition occurring when the body does not get enough blood flow
What are 4 main categories of shock?
- Cardiogenic –> due to heart problems
- Hypovolemic –> due to low total blood volume
- Obstructive –> due to blood flow obstruction outside the heart
- Distributive –> due to abnormal fluid distribution
What are 4 types of distributive shock?
- Anaphylactic
- Septic
- Neurogenic
- Endocrine
What is sepsis?
What is septic shock?
Sepsis = organ injury/damage in response to infection; leads to low BP and abnormal cellular metabolism
Septic shock = worsened sepsis to the point where BP cannot be maintained with IV fluids alone
What are common infections that are known to lead to septic shock? (10)
What percentage of septic shock is due to UTI? RTI? IV? Idiopathic?
- Appendicitis
- Pneumonia
- Bacteremia
- Diverticulitis
- Pyelonephritis
- Meningitis
- Pancreatitis
- Necrotizing fasciitis
- MSRA
- Mesenteric ischemia
UTI = 35%; RTI = 15%, IV = 15%, iatrogenic = 30+%
What is the name for toxins secreted by:
- Gram-positive bacteria
- Gram-negative bacteria
- Exotoxins, enterotoxins
- Endotoxins, lipopolysaccharides
Why does vasodilation occur in septic shock? (3)
- Toxins from bacteria cause direct endothelial injury and thus release of the vasodilator NO
- Toxins from bacteria activate the complement pathway which activates mast cells to release the vasodilator histamine
- Toxins from bacteria activate immune cells (macrophages/neutrophils) which release cytokines leading to vasodilation
Why does septic shock lead to decreased BP?
- Extreme systemic vasodilation
- Immune response causes leaky vessels which decreases intravascular volume
- Immune response causes endothelial damage which leads to clots
In septic shock, what does “low BP” mean?
SBP <90 mmHg
MAP <70 mmHg
SBP decreasing 40 mmHg or more without another cause
What are signs of end-organ dysfunction? (4)
- Kidney failure
- Liver dysfunction
- Changes in mental status
- Elevated serum lactate
What are symptoms of infection in SIRS?
- Fever (>38.0decC) or hypothermia (<36.0degC)
- Hyperventilaion (>20 bpm or PaCO2 <32mmHg)
- WBC < 4,000 cells/mm^3 or >12,000 cells/mm^3
- Tachycardia with HR > 90bpm
How is septic shock treated? (6)
- Give IV fluids (with albumin if large volume)
- Administer a broad spectrum antibiotic
- Administer vasopressors (NE + possibly Epi; angiotensin II in adults)
- Identify source and attempt to control it
- Support any major organ dysfunction (ex. dialysis)
- Get high fever under control
What is acute kidney injury?
What are the 3 categories of AKI?
Acute and sustained decrease in renal function causing either
- Increased serum creatinine by 44.2 umol/L
- Increase in serum creatinine by 20%
3 categories:
Prerenal = decreased renal perfusion; preserved tissue integrity
Renal = injury to the structures of the nephron
Postrenal = obstruction of collecting system
What are t
AKI epidemiology
- How many adults per year have AKI with a serum creatinine > 500 uM?
- How many adults per million have AKI with a serum creatinine > 300 uM?
- How many adults per million have renal replacement therapy a year due to AKI?
- What % of AKI is initially pre-renal?
- What 3 populations have increased risk for post-renal AKI?
- 172 million
- ~550/million
- 131/million
- 75%
- Prostatic disease, single kidneys, intra-abdominal/pelvic cancer
What are 4 categories of causes for pre-renal AKI? Please list examples in each category.
- Absolute fluid loss
- Ex. Major hemorrhage, vomiting, diarrhea, sever burns - Relative fluid loss
- Ex,. Distributive shock, CHF, decompensated liver cirrhosis - Local artery problems
- Ex. Renal artery stenosis, embolus, extrinsic compressionm, vasculitis - Exogenous cause
- Ex. NSAIDs, ACEI or ARBs in context of CHF, RAS, dehydration
What are 6 pathophysiological consequences that occur in pre-renal AKI?
- Azotemia
- Oliguria
- Edema
- Hypernatremia
- Hypertension
- Progression to ischemic acute tubular necrosis
What are 3 categories of causes for post-renal AKI? Please list examples in each category.
- Extrinsic compression
- Ex. Intra-abdominal tumor, prostatic tumor, BPH - Internal blockage
- Ex. Kidney stones, bladder stones, tumor inside the tract - Exogenous cause
- Ex. Obstructed urinary catheter
What are 6 pathophysiological consequences that occur in post-renal AKI?
- Oliguira
- Azotemia
- Hydronephrosis
- Edema from pressure
- Hypernatremia from pressure –> becoming hyponatremia as high pressures damage the lumen epithelium
- Hyperkalemia (on complete obstruction)
What are the 4 types of renal AKI?
- Vascular
- Glomerular
- Interstitial
- Tubular necrosis
What are causes of AKI?
Vascular (2)
Glomerular (3)
Interstitial (5)
Tubular necrosis (3)
- Vascular
- Microangiopathies (pre-eclampsia, DIC, vasculitis, HT), sickle cell disease - Glomerular
- Post-infectious glomerular nephritis, nephrotic syndrome, auto-immune destruction - Interstitial
- Drugs, chronic use of analgesics, DM, pyelonephritis, auto-immune destruction - Tubular necrosis
- Ischemia (pre-renal AKI), exogenous toxins (drugs, poisons), endogenous toxins (rhabdomyolysis, hemolysis, tumor lysis syndrome, oxalate, myeloma)
Describe the pathophysiology of tubular necrosis:
- Something causes necrosis of the tubular epithelium
- Dead epithelial cells slough into the tubule and build up, plugging the tubule
- This increases tubular pressure proximal the plug –> decreased GFR –> oliguria and azotemia
- This decreases tubular pressure distal to the plug –> RAAS –> edema, hypernatremia
- With more and more damage, less re-absorption and secretion occurs –> hyperkalemia, metabolic acidosis
Describe the pathophysiology of glomerulonephritis:
- Antigen-antibody complexes deposit in glomerular tissue
- This activates teh complement system which recruits more immune cells such as macrophages and neutrophils
- Immune cells release lysosomal enzymes which causes inflammation and damage of the podocytes
- Damaged podocytes allow protein tino the urine –> proteinura, hematuria
- Fluid leakage reduces pressure gradient driving filtration of the smaller molecules ane electrolytes and GFR actually goes down –> oliguira, azotemia
- The kidneys try to respond by activating RAAS –> hypertension, hypernatremia, edema
Fill in the following findings for pre-renal, renal, and post-renal AKI:
When is renal biopsy indicated in AKI? (4)
- Unexplained with 2 non-obstructed normal sized kidneys
- AKI in the presence of nephritic syndrome
- Systemic disease associated AKI
- Kidney transplant dysfunction
What is the first line imaging modality in AKI? What is used for F/U?
First line = renal U/S
F/U = MRI and CT (without contrast)
What post void residual value would suggest neurogenic bladder dysfunction?
>50-100mL
What are all the steps taken when managing/treating AKI?
- Prevent cardiovascular collapse/death and call a nephrologist
- Identify the underlying cause and try to treat
- Correct electrolyte imbalance
- Monitor kidney function
(Avoid NSAIDs, iodinated contrasts, some antibiotics)
What 7 groups are at risk for acute tubular necrosis as a post-surgical complication?
- Pre-existing renal impairment
- Hypertension
- Cardiac disease
- Peripheal vascular disease
- DM
- Jaundice
- Advanced age
What 2 drug categories are most frequently associated with drug-induced AIN?
Give 7 other examples:
- NSAIDs
- PPIs
Others =
- Cephalosporins
- Methicillins
- Fluoroquinolones
- Phenytoin
- Allopurinal
- 5-aminosalicylates
- Captopril
What are 4 theories for how drugs cause AIN via immune reactions?
- Drug serves as a hapten –> binds to endogenous protein making it antigenic
- Molecular mimicry
- Drugs become trapped in interstitium
- Drugs form a circulating immune complex which is deposited in the interstitium
What type of immune reaction is drug-induced AIN thought to be?
(2 possible types…cell vs. antibody)
Type I (IGgE) or IV (T cell) hypersensitivity
Cell-mediated immunity
What is a compliation of drug-induced AIN?
Scar tissue that permanently damages renal function
What are 6 presenting symptoms indicative of drug-induced AIN?
What are some other more general symptoms?
On U/S, what happens to echogenicity?
- Sudden impairment of renal function
- Mild proteinuria (not nephrotic)
- Abnormal urinalysis (hematuria, pyuria, leukocyte casts, eosinophils, leukocytes)
- Flank pain
- Normal BP
- No edema
General = malaise, anorexia, nausea, joint pain, skin rash
Echogenicity increases on U/S
How is drug-induced AIN diagnosed?
Must be confirmed with a kidney biopsy
- Dziffuse or patchy inflammatory infiltrates in the deep cortex and outer medulla
- Mostly T-cells, monocytes, and macrophages
- Few plasma cells, eosinophils, neutrophils
- Sparse, non-necrotic granulomas
- Possible tubulitis
- Interstitial edema between tubules
- Normal glomeruli
How is drug-induced AIN treated?
- Identification and withdrawal of the allergen
- Early treatment with corticosteroids for the first 5 days (prednisone)
- This is controversial
What are 6 indications for renal biopsy?
- Isolated/persistent hematuria
- Thought to come from glomerulus
- Combined with features of progressive renal disease - Prtoteinuria at high or increasing levels
- AKI when cause is unknown or thought to be acute nephritic syndrome
- Tumors
- Transplant
- Query connective tissue disease
What are contraindications for renal biopsy?
Absolute (5)
Relative (9)
Absolute = bleeding diathesis, uncontrolled HTN, active renal infection, small kidneys, no consent
Relative = solitary kidney, azotemia, uremia, anatomical abnormalities, polycystic, on anti-clotting meds, pregnancy, UTI, obesity
What are 6 risks associated with renal biopsy?
- Bleeding –> shock/anemia/transfusion risks/death
- Infection
- Damage to surrounding structures (bowel and bladder)
- Only getting scar tissue and needing to re-biopsy
- Allergies to materials used
- Formation of AV fistula
What is diabetic nephropathy? What values are used to evaluat it?
Chronic loss of kidney function occurring in those with DM
Evaluated via urine albumin excretion or reduction in GFR
- What % of those with DM type I will experience diabetic kidney disease?
- What % of DM type I deaths are due to diabetic kidney disease
- What % of those with DM type II will experience diabetic kidney disease?
- What % of DM type II deaths are due to diabetic kidney disease
- 15-40%
- 21%
- 5-20%
- 11%
What factors increase the risk and rate of acquiring diabetic kidney disease in those diagnosed with DM? (4)
- Poorly controlled hyperglycemia (A1C >7.5%)
- Poorly controlled high BP (>130/80)
- Smoking
- Family history
What is the general overview of the pathology behind diabetic kidney disease? (non-enzymatic glycosylation)
- Narrowing efferent arteriole from vessel glycation (hyaline arteriosclerosis) causes increased pressure in the glomerulus
- In response to increased glomerular pressure there is afferent arteriole dilation and mesangial ECM expansion –> thickened basemenet membrane
- The basement membrane thickening stretches out the podocytes, which allows proteins to slip into the urine
- Overall there is hyperfiltration
- Over time, the increased pressure causes tissue injury which develops into fibrosis.
- Fibrosis leads to decreased filtration and proteins, creatinine, water, etc. build up in the blood
- Kidney function declines into CKD and eventual ESRD
Explain the process of non-enzymatic glycosylation and how it leads to diabetic nephropathy:
Other than non-enzymatic glycoslyation, briefly outline other ways that diabetes contributes to kidney injury. (6)
- Sorbitol pathway –> ROS and decreased anti-oxidant capacity –> cellular damage
- Sorbitol pathway –> osmotic stress –> cellular damage
- Diacylglycerol pathway –> increased transcription of ECM, fibronectin, collagen –> fibrosis
- Hypoxia from increased metabolism –> HIF-1 activtaion –> collagen and fibtronectin production –> fibrosis
- Decreased NO production
- Increased prerenin receptors on podocytes in the presence of hyperglycemia –> more activation of RAAS
Explain the findings in GFR and proteinuria over the course of diabetic kidney disease:
What are 9 symptoms of diabetic nephropathy? Why do they occur (brief explanation).
- Nocturia and frequent day time urination (during hyperfiltration stage)
- Foamy urine (from proteinuria)
- Tiredness (from hypoalbuminemia and uremia)
- Headaches (from increased systemic BP)
- Nausea and vomtigin (from uremia)
- Lack of appetite (secondary to nausea and vomiting)
- Uremic frost (from urea depositing in skin)
- Itchy skin (from urea collecting in the skin)
- Leg swelling (from hypoalbuminemia, RAAS)
What are some end stage complications of diabetic nephropathy? (8 categories)
- Uremia –> lethargy, pericarditis, encephalopathy
- Decreased Epo –> anemia
- Iron deficiences –> anemia, inflammation, bone marrow suppression
- Fluid retention –> pulmonary edema
- Hyperphosphatemia –> vascular calcification
- Hyperkalemia –> muscle cramps, cardiac arrhythmias
- Decreased calcitriol and vitamin D –> hyperparathyrodisim, vascular calcification, osteodystrophy
- Metabolic acidosis
How is diabetic nephropathy prevented?
How is it “treated”?
- Screening = yearly (wait 5 years after diagnosis for type I)
- Hypertensive medications (ACEI, ARB, vasopressor, Ca++ channel blocker)
- Dyslipidemia medication (statins)
- Hyperglycemic medications (sulphonylureas, glitazones, SGLT2 inhibitors, DPP4-inhibitors, GLP-1s, metformin)
The closest thing to treatment is renal replacement therapy (transplant or dialysis)
Define chronic kidney disease:
A group of disorders affecting the structure and function of the kidney and causing a decline in glomerular filtration rate and irreversible loss of nephrons over 3+ months
What is the diagnostic criteria for CKD? (2)
- Kidney damage for 3+ months (structural/functional abnormalities of the kidney) with or without decreased GFR
- GFR <60 mL/min/1.73m^2 for 3+ months with or without kidney damage
What is the GFR for the following CKD stages:
G1, G2, G3a, G3b, G4, G5
What is the albuminuria for the following CKD stages:
A1, A2, A3
G1 = 90+
G2 = 60-89
G3a = 45-59
G3b = 30-44
G4 = 15-29
G5 = <15
A1 = <30 mg/g
A2 = 30-300 mg/g
A3 = >300 mg/g
What health conditions are at increased risk of CKD? (6)
Diabetes
Hypertension
Obesity
High cholesterol
Lupus
Cardiovascular disease
Previous episode of AKI
Structural abnormalities of the urinary tract
(Family history)
What races are at increased risk of CKD? (4)
African Americans (Apo-1 mutation)
Indigenous Peoples
Hispanics (sugar cane workers)
South Asians (Pakistan, Sri Lanka, Bangladesh, India)
What are the 4 categories of causes of CKD?
- Vascular
- Glomerula
- Tubulointerstitial
- Cystic (PCKD)
What are 5 vascular causes of CKD?
- Renal artery stenosis from FSGS
- Renal artery atherosclerosis
- Hypertension
- Vasculitis
- Microangiopathy
What are 7 glomerular causes of CKD?
- Primary nephritis from IgA
- Autoimmune disease
- Connective tissue disease
- Malignant disease
- Drugs (NSAIDs, tobacco)
- Hyperfiltration
- Systemic infection
What are 7 tubulointerstitial causes of CKD?
- Autoimmune disease
- Connective tissue disease
- Granulomatous disease
- Drugs
- Obstructive nephropathy
- Chronic infection
- Post-AKI
How does hypertension cause CKD?
- High pressure causes thickening of all arteries to withstand the pressure, including the afferent arteriole
- Narrowed afferent lets less blood into the glomerulus
- Less blood causes ischemic injury
- Immune cells respond to the injury and release TGF-beta
- TGF-beta causes mesangial cells to regress to mesangioblasts which secrete ECM. This ECM causes glomerulosclerosis
- The more nephrons that are lost, the higher the GFR gets in remaining nephrons
- Overtime more and more nephrons are lost until there is complete failure.
What are the physiological consequences of CKD?
- Oliguria
- Azotemia
- Hyperkalemia
- Hyperphosphatemia
- RAAS activation
- Hypocalcemia
- Anemia
- Metabolic acidosis
What are 3 causes for hyperkalemia in CKD?
- Decreased secretion of sodium in the tubule due to cellular damage and lowered GFR
- RAAS activation
- Metabolic acidosis
What is the presentation of azotemia? (8)
- Nausea/vomiting, loss of appetite
- Hiccoughs, cramps (neuro)
- Encephalopathy/asterixis/coma/death
- Pericarditis
- Increased risk of bleeding
- Uremic frost
- Amenorrhea from decreased estrogen
- Impotence from decreased testosterone
What 4 things are investigated during CKD?
- GFR
- Albuminemia
- Kidney biopsy
- Renal U/S
What are 4 serious complications of CKD?
- Anemia of chronic kidney disease (from decreased production of Epo)
- Secondary hyperthyroidism and bone marrow disease due to elevated phosphorous and low calcium stimulating PTH
- Volume overload causing pulmonary edema
- Metabolic acidosis
What “treatment” is available for CKD?
- Prevention of progression (statins, aspirin, ACEI, ARB, oral DM meds, low protein diet)
- Immunosuppression (corticosteroids/cyclophosphamide) when relevant
- Ferrous gluconate for anemia
- Dialysis
- Renal transplant
What does a CKD diet look like? (9 things)
- Adequate calories to maintain weight (and not lose)
- Low protein diet (ex. carbs, fruit, veggies)
- Low fat/unsat fat diet (ex. olive/peanut/corn oils)
- Only “healthy” carbs low in K+ and P(3-)
- Low sodium (fresh food, no pickles/condiments)
- Low potassium (apples, cauliflower, white bread, beef, chicken)
- Low phosphorous (Italian bread, corn, light soda)
- Limited fluids (less soup, ice cream, watery fruits/veggies)
- Supplements (vitamin D, water-soluble vitamins)
What are the upper limits for potassium, sodium, phosphorous, and protein in a CKD diet?
Compare peritoneal and hemo dialysis:
Define dialysis and give 3 situations in which it is indicated:
Process of removing excess water, solutes, and toxins from the blood in those whose native kidneys can’t do this naturally
AKI, CKD stage 5, ESRD
What are 3 ways to access the blood in hemodialysis?
- Primary arteriovenous fistula (usually lower arm)
- Synthetic bridge graft
- Central venous catheter (dialysis line)
What are the indications in AKI that dialysis is needed? (6)
A = acidemia unresponsive to meds
E = electrolyte abnormalities unresponsive to meds
I = intoxication (salicylic acid, lithium, isopropanol, Mg+ laxatives, ethylene glycol)
O = fluid overload unresponsive to diuretics
U = uremia complications (pericarditis, encephalopathy, GI bleeding)
BUN > 80-100 mg/dL
What are the indications in AKI that dialysis is needed? (10)
1-5 = AEIOU
- Refractory accelerated hypertension
- Persistent severe nausea/vomiting
- Creatinine clearance <7-10 mL/min
- BUN > 36 mM
- Heart concerns
What are some absolute contraindications for peritoneal dialysis? (8)
- Type II ultrafiltration failure
- Severe IBD
- Acute active diverticulitis
- Abdominal abscess
- Active ischemic bowel disease
- Severe active psychotic disorder
- Marked intellectually disability
- Third trimester of pregnancy
What are some relative contraindications for peritoneal dialysis? (8)
- Severe malnutrition
- Multiple abdominal adhesions
- Infection
- Proteinuria > 10g/day
- Demenita
- Physical barriers (amputation, obesity, blindness, homeless)
- Depression
- Ostomy
What are some absolute contraindications for hemodialysis? (2)
- Unconsenting/uncooperative patient
- Hemodynamically unstable patient
What necessitates amputations in many diabetics?
- Peripheral artery disease –> reduced blodo flow –> reduced healing
- Neuropathy –> reduced feeling –> undetected wounds
- Skin changes –> skin breaks more easily
Together this causes damage that persists until gangrene and osteomyelitis occurs
What are 7 complications post-amputation?
- Hematoma
- Phantom limb sensation/pain
- Re-perfusion injury
- Sepsis
- Failure to heal
- Depression
- DVT
Fill in the following chart regarding steroid hormone synthesis:
What is congenital adrenal hyperplasia? (CAH)
A group of autosomal recessive disorders involving a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, and androgens.
Fill in the following chart regarding four different types of congenital adrenal hyperplasia:
What is the prevalence of CAH in the general global population?
What 2 populations are at increased risk of classic CAH?
What 2 populations are at increased risk of non-classic/mild CAH?
General = 1/15,000
Classic = Yupic Eskimos of Alaska, French Island of La Reunion
Non-classic/Mild = Hispanic, Ashkenazi Jews
What is the difference between classic, simple, and non-classic CAH?
Classic = severe form
Simple = mild form
Non-classic = very mild form
What types of CAH lead to excess androgen? (2)
What is the presentation in someone with excess androgen?
- Males (2), Females (6), Both (5)
21-hydroxylase and 11-beta hydroxylase deficiencies
Males
- Functional penis but without sperm
- Normal to enlarged penis
Females
- Ambiguous genitalia
- Menstrual irregularity in adolescence
- Infertility due to anovulation
- Clitoromegaly
- Shallow vagina
- Hirsutism
Both
- Early pubic hair
- Rapid growth in childhood
- Precocious puberty or sexual infantilism
- Excessive facial hair
- Accelerated linear growth and skeletal maturation
What types of CAH lead to insufficient androgen/estrogen? (2)
What is the presentation in someone with insufficient androgen/estrogen?
- Males (2), Females (4)
17-alpha hydroxylase and 3-beta hydroxysteroid dehydrogenase deficiency
Males
- Undervirilization
- Apparently female external genitalia
Females
- Sexual infantilism or abnormal pubertal development
- Infertility
- Amenorrhea
- Lack of breast development
What types of CAH lead to excessive mineralocorticoids? (2)
What is the presentation in someone with excessive mineralocortiocids? (7)
17-alpha hydroxylase and 11-beta hydroxylase deficiency
- Sodium retention (volume overload and edema, hypertension, CV complications)
- Hypokalemia
- Metabolic alkalosis
- Decreased adult height
What types of CAH lead to insufficient mineralocorticoids? (2)
What is the presentation in someone with insufficient mineralocortiocids? (7)
3-beta HSD, 21-alpha hydroxylase deficiency
- Hyponatremia (vomiting, hypotension, hyperkalemia, dehydration, death)
- Hyperpigmentation of genitalia and areolae
What are the lab investigations in CAH?
What types of imaging are done in CAH?
- CT scanning to exclude bilateral adrenal hemorrhage (acute onset)
- Pelvic U/S to identify uterine or renal anomalies (ambiguous genitalia)
- Urogenitography to define the anatomy of the internal genitalia
- Bone-age study to evalue advanced skeletal maturation (precocious pubic hair, clitoromegaly, accelerated growth)
What are 5 complications of CAH?
- Salt-wasting –> morbidity from hyponatremia, hyperkalemia, dehydration, and hypotension
- Concerning in males with 21-alpha hydroxylase whose external genitalia look ~normal - Lack of GCs during illness/trauma/surgery –> morbidity
- Increased viral infection susceptibility
- Short stature
- Infertility
How is CAH treated/managed?
- IV bolus of isotonic NaCl if there is hyponatremia and dehydration
- Stress dosage of hydrocortisone every 6 hours
- Dextrose in rehydration fluid if there is hypoglycemia
- ST GC therapy for MC deficiency
- LT GC and MC therapy for GC and MC replacement
- Androgen suppression if there is excess androgens
- Exogenous testosterone and/or estrogen if there is insufficient androgens
- Surgery for clitoral recession and vaginoplasty
(Dexamethasone is used in CAH female fetuses but doesn’t treat the condition and may cause cognitive behavioural defects)
What is androgen insensitivity syndrome?
What are the 3 types?
An X-linked recessive condition resulting in a failure of normal masculinization of the external genitalia in XY individuals; an intersex condition
- Complete = normal extermal female genitalia
- Partial = ranges from mildly virilized female to mildly undervirilized male external genitalia
- Mild
What is the internal sexual organs in Androgen Insensitivity Syndrome?
Testes present but undescended (SRY still present)
Improper epididymis, vas deferens, and seminal vesicles (testosterone can’t act on Wolffian ducts properly)
No fallopian tubes, uterus, or upper vagina (anti-Mullerian hormone still present)
What is the overall prevalence of AIS?
What is the incidence of CAIS? PAIS?
AIS = 1/20,400
CAIS = 1/99,000
PAIS = 1/130,000
What causes androgen-insensitivity syndrome?
Loss of function mutation in the androgen receptor gene
- Multiple different possible mutations, either complete deletion, partial deletion, point mutation, or small insertion
What is the presentation of complete androgen-insensitivity syndrome?
Female genitalia
Lack of pubic or axiallyar hair
Lack of acne
Absence of voice change
Low bone mineral density
Infertility
Female secondary sex characterisitcs
Reduced clitoral length
Possible inguinal masses (which are the undescended testes)
What is Kennedy Disease?
A motor neuron disease caused by a CAG expansion in the androgen receptor gene; leads to spinal and bulbar muscular atrophy, post-pubertal gynecomastia, reduced fertility, possible sensory deficits, and decreased facial hair growth
What are possible investigations in the work up for androgen-insensitivity syndrome
- Karyotype
- FISH probles for the SRY region of the Y chromosome
- Testosterone and DHT levels (expect high)
- Mutation analysis of AR
- Pelvic U/S to identify Wolffian or Mullerian structures
- Histology of the testes (biopsy)
What are 4 complicat ions associated with androgen-insensitivity syndrome?
- Increased risk of tesitcular malignancy if testes are not removed (CAIS)
- Increased risk of germ cell tumors if testes are not removed (PAIS)
- Pyschological morbidity
- Osteoporosis
What are the 3 main categories of treatment for androgen-insensitivity syndrome? Give examples of each.
- Surgery - orchidectomy, vaginal lengthening, cosmetic reconstructive
- Hormone replacement therapy - estrogen replacement is CAIS, estrogen or testosterone/DHT replacement in PAIS
- Psychological support (parental genetic counseling, pediatric psychologists, AIS support groups)
What are 6 different cultures that practice consanguinity?
- North African
- West Asian
- South Indian
- Pakistan
- Turkey
- Lebanon
What is precocious pubrerty? What are the two main categories?
Progression through the Tanner Scale before 95% of children that age.
- Central/Gonadotropin-dependent = abnormality located in the brain
- Peripheral/Gonadotropin-independent = abnormality located in the gonads or adrenal glands
What are 5 causes of central / gonadotropin-dependent precocious puberty?
- Brain tumor (hypothalamic hamartoma, langerhans cell histiocytosis, hCG releasing tumor)
- Prior infection (CNS TB)
- Brain trauma (radiation, injury, hydrocephalus)
- Brain abnormalities
- Idiopathic
What are 5 causes of peripheral / gonadotropin-independent precocious puberty?
- Tumors and cysts (Sertoli-Leydig, Granulosa-Theca tumors, germ cell tumors)
- Genetics (McCune Albright, FMPP, aromatase excess, 21/11beta-OH-deficiency)
- Hypothyroidism (Van Wyk and Grumbach syndrome)
- Environmental exogenous hormoens
- Iatrogenic meds/creams containing sex hormones
What are 4 possible investigations to order for the presentation of precocious puberty?
- GnRH agonist stimulation test (done first)
- Increased FSH/LH = central cause
- Normal FSH/LH = peripheral cause - Blood tests (elevated or normal LH/FSH)
- Imaging with U/S or MRI of the brain/gonads (tumors, size, cysts, abnormalities)
- Bone Age X-Ray
What are 6 complications (including increased risks) associated with precocious puberty
- Early fusion of epiphyses leading to reduced final stature
- Slipped capiital femoral epiphysis
- Increased risk of sexual abuse
- Pscyhological damage
- Increased risk of breast cancer in females
- Increased aggressiveness in males
What are the 3 treatment options for precocious puberty?
- GnRH analogues to over-express GnRH, effecgively suppressing LH and FSH –> used for central causes
- Antagonists to estrogen or testosterone –> used for peripheral causes
- Sugery to remove any cysts or tumors
What is delayed puberty?
What are the 3 different categories?
Lack of progression through the Tanner scale by the time 95% of children that age have begun to sexually mature (post 13 in females and post 14 in males)
- Primary hypogonadism / hypergonadotropin hypogonadism = decreased sex steroids due to a gonadal dysfunction
- Secondary hypogonadism / hypogonadotropin hypogonadism = decreased sex steroids due to a brain dysfunction
- Constitutional delay = a natural non-pathologic delay
What are 5 acquired and 5 congenital causes of hypergonadotropin hypogonadism?
Acquired:
- Radiation
- Chemotherapy
- Physical trauma to the gonads
- Surgery
- Infection
Congenital
- Klinefelter syndrome
- Turner syndrome
- Noonan syndrome
- XY with SRY gene-immunity
- Autoimune disorders
What are 8 acquired and 2 congenital causes of hyporgonadotropin hypogonadism?
Acquired:
- Radiation
- Chemotherapy
- Physical trauma to the brain
- Tumor causing decreased GnRH, prolactinoma, or hyperthyroidism
- Excess exercise
- Malnutrition
- Obesity
- Stress
(9. Chronic illness)
Congenital:
- Kallman syndrome
- Panhypopituitarism
(3. Chronic illness)
What are 5 possible investigations to complete in the work up for delayed puberty?
- Bone age X-ray
- GnRH agonist stimulatory test
- Medical and family history
- Imaging using U/S or MRI of the brain and gonads (abnormalities, trauma, tumors, etc.)
- Physical exam to examine development
What are 3 treatments/ managements in delayed puberty?
- Hormone replacemen therapy
- Surgery to remove a tumor
- Infertility treatment to make reproduction possible if appropriate
What is skewed X-inactivation and when does it occur?
When X-inactivation occurs in cells at a 90:10 ratio
- Silencing of an abnormal X chromosome
- Silencing of a normal X chromosome due to the other containing an abnormal autosomal translocation
- (Random process 5-10% of the time)
What is Turner syndrome?
What are 3 of the more common symptoms?
A genetic condition in which a female is partly or completely missing an X chromosome, leading to a plethora of possible symptoms that usually present in a unique way
- Short stature
- Webbed neck
- Infertility
What % of fetuses with Turner syndrome are born live?
How many females at birth are born with Turner’s? (1 in ?)
99% are spontaneously aborted while 1% are born alive.
1/2000 to 1/5000
How does Turner syndrome arise? (3 ways)
What parent more often contributes the abnormal gamete?
- The parent has a balanced translocation of the X chromosome and thus presents as asymptomatic
- The mother has 45,X-mosacism affecting her maternal germ cells
- Non-disjunction in the paternal cells, either at meiosis 1 or 2
Paternal cells more often contribute the abnormal gamete
What causes the symptoms of Turner’s syndrome?
The presence of only one pseudoautosomal region
List visible alterations seen in Turners syndrome (16)
- Short stature
- Lymphedema of hands and feet
- Broad chest with widely spaced nipples
- Low posterior hairline
- Low-set ears
- Increased weight / obesity
- Shortened metacarpal (IV)
- Hypoplastic or hyperconvex nails; small nails
- Webbed neck
- High waist to hip ratio
- Microagnathia
- Cubitus Valgus
- Palmar crease
- Drooping eyelids
- Increased number of “birthmarks”
- Madelung deformity of the wrist
What are some physiological abnormalities seen in Turners Syndrome? (15)
- Rudimentary ovaries/ gonadal streak –> infertility and amenorrhea
- Aoertic valve stenosis
- Coarctation of the aorta
- Bicuspid aortic valve
- Hypoplastic left heart syndrome
- Partial anomalous venous drainage
- Persistent hypertension
- Aortic root dilation –> increased risk of aortic dissection/rupture
- Horseshoe kidney
- Abnormal urine collecting system
- Visual impairments
- Ear infections –> hearing loss
- ADHD
- Nonverbal learning disability (maths, social, spatial)
- Red-green color blindness
What are those with Turner’s syndrone at increased risk of? (think general) (6)
- Kidney abnormalities
- CV abnormalities
- Bacterial endocarditis
- Skeletal abnormalities
- Diabetes
- Hypothyroidism (often from Hashimoto’s hypothyroidism
What are possible prenatal screening techniques for Tuner’s syndrome? (3)
- Amniocentesis (with QFPCR)
- Chorionic villus sampling (with FISH for X)
- Abnormal U/S findings (heart defects, kidney abnormalities, cystic hygroma, ascites)
What investigations can be done postnatally for Turner’s syndrome? (8/10)
- Physical exam for the known symptoms
- Karyotyping (choice of test)
- Y-centromeric probe
- LH/FSH (high <4 and >10; normal between 4-10)
- TSH indicating hypothyroidism
- Bone age (delayed after adolescence)
- U/S for kidney/collecting system abnormalities
- Echo or MRI for heart and aorta abnormalities
(9. Audiology testing for hearing loss)
(10. Urinalysis for DM)
What can be done for the management of Turner’s syndrome?
- GH +/- androgens starting at age 8 –> increase growth
- Estrogen replacement at age 12-15 for bone strength, CV health, and pubertal changes
- Thyroid hormones if necessary
- Cosmetic surgery
- Prophylactic antibiotics before any dental/surgical procedure
- Reproductive technology
- Calcium and vitamin D supplements
- Antihypertensive agents
- Physical activity and healthy diet
What is premature ovarian failure / primary ovarian insufficiency? What are two major categories?
The loss of function of the ovaries before the age of 40.
- Follicle depletion (low initial # or accelerated atresia)
- Follicle dysfunction
What is secondary ovarian insufficiency?
Loss of function of the ovaries before age 40 due to inadequate gonadotropin stimulation from inadequate LH/FSH production
What are 10 causes of POF due follicualr depletion?
- Disrupted germ cell formation
- Thymic hypoplasia or aplasia inhibiting noral endowment of primordial follicles
- X chromosome monosomy/aneuploidy (X0, XXX)
- X chromosome mutations
- Galactosemia
- Cytotoxic therapy
- Irradiation
- Inflammation
- Auto-immune conditions
What are 9 causes of POF due follicualr dysfunction?
- Idiopathic
- Enzyme deficiencies (cholesterol desmolase, 17-alpha-OH)
- FSH/LH receptor mutation
- FSH receptor-blocking antibodies
- Pseudohypoparathyroidism preventing cAMP production for signaling
- Autoimmune oophoritis
- Polyglandular autoimmune syndromes
- Other immune disease (Hashimoto, DM type I, Vitiligo, Lupus, Sjögren, rheumatoid arthritis)
- Infection
What is the pathophysiology of POF?
- Reduced/depleted follicle number or dysfunctional follicles leads to decreased production of progesterone, estrogen, and inhibin
- This causes disinhibition of FSH and LH
- As a result, normal follicular development will not occur
- Overall estrogen further decreases and anovulation results
- LH and FSH levels are increased by the HPOU axis to no avail.
How do cysts form as a result of POF?
A lonely follicle may develop in the presence of high FSH, even though estrogen levels are low. However, the high LH will cause luteinization which may then persist as a cystic structure.
How does POF present?
- Missed or infrequent periods
- Difficulty conceiving or complete infertility
- Hot flashes and night sweats
- Vaginal dryness with dyspareunia
- CV disease
- Osteoporosis
What investigations are done in the work up for POF and its possible cause? What are possible results? (9)
- Serum or urine beta-hCG for pregnancy
- Serum FSH/LH levels –> both elevated, with FSH usually greater than LH (2x, 1 month apart)
- Karyotype showing any X abnormalities
- Genetic testing showing any known mutations associated
- Antibody testing for adrenal or steroid cell antibodies
- Ovarian U/S showing lack of follicles
- Pituitary/hypothalamus MRI (rule out secondary ovarian failure)
- DEXA for bone mineral density
- Work up for other immune diseases (Adrenal antibodies, Antinuclear antigen antiboies, rheumatoid factors, thyroid peroxidase antibodies)
What is the management plan for POF?
- Hormone therapy with estrogen/progestin and possible androgen
- In vitro fertilziation using a donor egg
- Calcium, vitamin D supplementation
- Weight-bearing exercise for 30 minutes per day, 3 days a week
What is the difference between primary and secondary amenorrhea?
Primary amenorrhea = the absence of menarche
Secondary amenorrhea = amenorrhea for 3 consecutive cycles when a woman has had menstrual cycles in the past
What are the 4 most common causes of secondary amenorrhea?
- Pregnancy (implantation increases progesterone, preventing menstruation)
- Hypothyroidism (increases AP activity and thus prolactin)
- Prolactin disorders (prolactinemia, prolactinoma)
- Medications (atypical antipsychotics)
Fill in the following chart for how to investigate common causes of secondary amenorrhea.
What are some possible causes of secondary amenorrhea? (16)
- Pregnancy
- Hypothyroidism
- Prolactinoma / Prolactinemia
- Atypical antipsychotics
- Emotional stress
- Anorexia and/or extreme exercise
- AP adenoma
- Sheehan’s Syndrome
- Apoplexy of the AP
- Savage (Resistant Ovarian Syndrome)
- Menopause
- POF/ POI
- Autoimmune damage of the ovaries
- Asherman’s syndrome
- Ablation of the endometrius
- PCOS
How do you narrow down what is causing a secondary amenorrhea?
Describe the progesterone challenge test:
- Deliver progestin (Provera) 10 mg for 5 days (usually oral but can be IM)
- After progestin, monitor for bleeding
- If bleeding occurs between 2-7 days after progestin is stopped:
- There is adequate estrogen in the body
- There is functional anatomy
- There is an anovulatory condition such as low progesterone or high androgen - If bleeding does not occur, give estrogen and progesterone together for 21 days
- If bleeding occurs afterwards:
There is inadequate signaling –> a problem with the HPOU
- If bleeding does not occur:
- There is an endometrial problem
Define oligomenorrhea
Infrequent or very light menstruation in a woman who once had regularly established periods
Periods occurring at intervals of greater than 35 days
Having 4-9 periods per year
What is the female athlete triad?
A syndrome characterized by:
- Eating disorder / energy deficiency
- Amenorrhea / oligomenorrhea
- Decreased BMD
What can cause the female athlete triad?
- Sports that emphasize low body weight
- Vegetarian diets
- Psychological predispositions
- Social factors (family, self-esteem, abuse)
- Genetics
What are some symptoms of the female athlete triad? (9)
- Disordered eating
- Fatigue
- Hair loss
- Cold hands and feet
- Dry skin
- Noticeable weight loss
- Increased healing time from injuries
- Increased incidence of bone fracture
- Amenorrhea / oligomenorrhea
What are some possible findings in someone with female athelete triad? (9)
- Elevated carotene in the blood
- Anemia
- Orthostatic hyotension
- Irregular electrolytes
- Low estrogen
- Vaginal atrophy
- Bradycardia
- Mildly elevated cortisol
- Low serum insulin and IGF-1
What are possible things that can be done for someone with female athlete triad?
- Diet change
- Reduced exercise
- Oral contraceptives
- HRT
- Mental health therapy
- Calcium and vitamin D supplements
- Bisphosphonates
- Anti-depressents, benzodiazepines
- Exogenous Kiss-peptin
- Potassium supplements
What is functional hypothalam amenorrhea (FHA)
Amenorrhea as a result of low energy availability, either as a result of decreased caloric intake, excessive energy use, increased stress, or a combination.
What is nondisjunction in meisosis and what types of cells are created as a result?
Abnormal separation of chromosomes in meiosis I or sister chromatids in meiosis II
If it happens in meiosis I –> 2, 2, 0, 0 copies of genes
If it happen in meiosis II –> 1, 1, 2, 0 copies of genes
What is monosomy? Give an example.
What is trisomy? Give 6 examples.
Monosomy = joining of a normal gamete with a gamete having no chromatids
- Ex. = Turner syndrome (X0)
Trisomy = joining of a normal gamete with a gamete having 2 chromatids
- Ex. = Down syndrome (21), Patau syndrome (13), Edwards syndrome (18), Klinefelter syndrome (XXY), Triple X syndrome (XXX) , XYY syndrome
What is nondisjunction in mitosis and what types of cells are created as a result?
The abnormal separation of chromatids during anaphase
Creates one cell with 3 copies of affected genes and one cell with 1 copy of affected genes
What is anaphase lag?
When something impairs movement of a chromatid during anaphse of mitosis, leading to its exclusion and loss from both daughters (one cell with 2 copies and one cell with 1 copy)
What is endoreduplication?
When chromosomes duplicate but the cell does not divide, creating polyploid cells (binucleated) cells with 4 copies of chromosomes
What is a hyrocele?
A pathological collection of serous fluid in the tunica vaginalis caused by injury and inflammation
What is a variocele?
Swelling in the scrotum due to dilation of the veins that drain the testes
What is infertility defined as?
The inability to reproduce by natural means after one year of unprotected intercourse
What are the most common causes of female infertility? (6)
- Ovulatory disorders
- Endometriosis
- Pelvic adhesions
- Tubal blockage
- Other tubal abnormalities
- Hyperprolactinemia
What are 3 ovarian causes of female infertility? (list sub-causes if possible)
- Ovulatory disorders (pituitary damage, Kallman’s, hyperprolactinemia, stress)
- Oocyte aging (smoking, radiation, chemo, autoimmune)
- Ocarian cysts (endometriosis, PCOS)
What are 6 fallopian tube/pelvic adhesion causes of female infertility? (list sub-causes if possible)
- PID (chlamydia, gonorrhea)
- Endometriosis
- Adhesions from previous surgeries/infections (appendicitis, IBD)
- Tb of fallopian tubes
- Salpingitis isthmica nodosa = diverticulosis of fallopian tubes
- Previous ectopic pregnancy
What are 4 uterine causes of female infertility? (list sub-causes if possible)
- Müllerian anomalies
- Endometrial polyps
- Intrauterine adhesions (D&C, C/S, myomectomy, Tb, idiopathic)
- Deficient progesterone = luteal phase defect (pituitary problems)
What are the 7 classes of Müllerian anommalies of the uterus?
1 = Uterine hypoplasia and/or agenesis
2 = unicornuate uterus
3 = uterus didelphys
4 = bicornuate uterus
5 = spetate uterus
6 = arcute uterus
7 = diethylstilbestrol (DES) drug related
What are 2 cervical causes of female infertility? (list sub-causes if possible)
- Congenital abnormalities
- Trauma (accident, surgery, parturition)
What are 6 causes of female infertility that are not due to the female reproductive tract
- Turner syndrome
- Antiphospholipid syndrome
- Celiac disease (possibly)
- BMI <19
- Kidney failure
- Liver failure
What are 7 diagnostic tests for investigating the cause of female infertility?
- Mucous stretch test = measure stretch of cervical mucous after sex
Hostile mucous will stretch <6cm, have no sperm, and/or have a negative Fern test
- Ovulation work up
Anovulation indicated by no increase in basal temperature at day 14, no luteal progesterone elevation, and/or abnormal LH/FSH/estrogen
- U/S to look for # of follicles, malformations, and endometrial lining
- Measure Anti-mullerian hormone
- Citrate test = inducing ovulation
- Sonohistiogram to check patency, polyps, and fibroids
- Laparascopic biopsy of endometrium to look for endometriosis
What are some treatment options for female infertility? (7)
- Administer clomiphrine citrate, which is an anti-estrogen, to trigger ovulation
- Give estrogen/progesterone (OCP) to fix endometriosis if that’s the problem
- Inject gonadotropins if deficient
- Perform intrauterine insemination
- Perform in vitro fertilization
- Gestational donor
- Surgery
Define the following:
- Oligozoospermia
- Asthenozoospermia
- Teratozoospermias
- Azoospermia
- Low number of sperm cells in the ejaculate (low [C])
- Decreased sperm motility
- Abnormal sperm morphology
- Absence of sperm cells in the ejaculate
What are the 4 categories of causes of male infertility
- Idiopathic
- Pre-testicular (endocrine and systemic)
- Testicular
- Post-testicular (sperm transport)
What are 8 pre-testicular causes of male infertility? (list sub-causes if possible)
- Hypogonadotropic hypogonadism (tumor, surgery, rads, chemo, trauma, vascular lesions, infiltrative disease, lymphocytic hypophysitis, Kallmann)
- Hyperprolactinemia (prolactinoma, exogenous dopamine antagonist)
- Panhypopituitarism
- PAIS
- CAH
- Genetics affecting LH/FSH secretion (Prader-Willi, Lowe Oculocererbral, Familial cerebellar ataxia, Laurence-Moon-Biedl)
- Drugs (estrogen, chronic glucocorticoids, opioids)
- Obesity
What are 13 testicular causes of male infertility? (list sub-causes if possible)
- Idiopathic dysspermatogenesis
- Tumors
- PAIS
- Cryptorchidism
- Vanishing testes syndrome
- Orchiditis (mumps, Tb, STDs, leprosy)
- Varicoceles
- Anti-sperm antibodies
- Testicular damage (torsion, surgery, rads, chemo)
- Testicular ischemia (CKD)
- Genetic conditions (Klinefelter, Y chromosome mutations, DAZL polymorphisms, Myotonic dystrophy)
- Drugs (antiandrogens, cyclophosphamide, estrogens)
- Environment (smoking, hyperthermia, lead)
What are 7 post-testicular causes of male infertility? (list sub-causes if possible)
- Epididymis abnormalities (estrogen, obstruction, trauma)
- Vas deferens abnormalities (gonorrhea, chlamydia, Tb, ligation, congenital absence)
- Ejaculatory disorders (DM, neuropathy, spinal trauma)
- Chronic infection of accessory glands
- Cystic fibrosis
- Primary ciliary dyskinesia
- Sexual dysfunction (organic, psychogenic)
Fill in the following chart for normal results of a semen analysis:
What are 4 variables looked at in semen microscopy?
- Sperm (concentration, count, motility, morphology)
- Debris/agglutination
- Leukocyte count
- Immature germ cells
What investigations are done to determine the cause of male infertility? (6)
- History (sexual development, sexual history, systemic illness, trauma, infections, surgery, drugs, environment)
- Physical (thyroid signs, Cushing’s signs, external genitalia)
- Semen analysis
- Endocrine testing of LH/FSH/testosterone
- Imaging of accessory glands/ducts
- Genetic testing
What are 5 possible treatments for male infertility?
- Antibiotics (if caused by infection)
- Hormone replacement therapy
- Lifestyle changes (avoid long hot showers, wear loose underwear)
- Artificial insemination (intrauterine insemination, in vitro fertilization, intro-cytoplasmic sperm injection)
(5. Donor sperm)
What is pelvic inflammatory disease?
An infection of the upper part of the female reproductive system (uterus, fallopian tubes, ovaries, inside pelvis)
What causes PID?
Infectious organisms (usually anaerobic and facultative bacteria)
- Most commonly polymicrobial
- Most common bacteria are gonorrhea and chlamydia
- Other causative organisms are gardnerella, H. influenzae
List some preventative causes of PID? (9)
- Abstinence
- Using condoms
- Regular STI testing
- Hormonal combined OCPs (thickens mucus plug)
- Avoid vaginal activity after pregnancy until cervix closes
- Reduce number of sexual partners
- Take STI history from partners and encourage their testing
- Avoid recreational drugs
- Avoid vaginal douching
What may help infectious organisms to descend from the vaginal os to the higher structures? (5)
- Antibiotics affecting vaginal flora
- Opened cervix during menstruation
- Retrograde menstrual flow
- Rhythmic uterine contractions during orgasm
- Carried by sperm after intercourse
What immune mechanism of the boyd is most implicated in PID?
Complement
What are some symptoms of PID?
PID is often asynpmtomatic
- Fever
- Nausea/vomiting
- Severe pelvic/abdominal pain (dull, achy, crampy, bilateral, constant, few days after menstruation, worse with movement, <7 days)
- Abnormal vaginal discharge
- Unanticipated vaginal bleeding (often after sex)
What are 7 investigative procedures for PID? What results woudl you expect?
- Physical exam (cervical motion/uterine/adnexal tenderness, peritonitis signs)
- Lab studies (high WBC, ESR, bacteria, IgG, no UTI results, leukorrheal vaginal secretions)
- Transvaginal U/S = thick/fluid filled tubes, thick cilia, indistinct endometrial borders, oophoritis, multiple ovarian cysts, free pelvic fluid, pelvic abscesses, ill-defined uterus)
- Laparoscopy (tubal wall edema, visible hyperemia, exudate on tubal fimbriae)
- MRI (hydrosalpinx, multiple ovarian cysts, ill-defined ovaries, thick-walled masses)
- Culdocentesis (purulent fluid, leukocytes, bacteria)
- Endometrial biopsy (possible scarring, organisms)
What are 3 ways to diagnose PID?
- Laparoscopically
- Histopathologically
- Clinically (sexually active + pelvic/abdo pain + cervical/uterine/adnexal tenderness + no other reason)
What are complications of PID?
- Scarring leading to chronic pain, infertility, ectopics, or infertility
- Peritoneal inflammation causing scar tissue on external surface of liver
What are the 2 treatment options for PID?
- Antibiotics
- Cefoxitin or cefotetan + doxycycline
- Clindamycin + gentamicin
- Ampicillin or sulbactam + doxycycline - Surgery if indicated
- Simple drainage
- Adhesiolysis
- Copious irrigation
- Unilateral adnexectomy
What is ectopic pregnancy?
Implantation outside of the uterine cavity
- In the fallopian tube
- On the outside of the fallopian tube
- On the ovary
- On the abdominal wall
- On the outside of the bowel
Ectopic pregnancy
- What are 3 risk factors?
- What is the presentation?
- What investigations can you do?
- How do you treat?
- Tubal scarring, prior ectopics, IUDs
- Unilateral pelvic or lower abdominal pain; vaginal bleeding
- Speculum and bimanual, beta-hCG low for GA, U/S showing adnexal mass
- Stabilize (fluid, blood, vasopressors); surgical laparotomy with possible salpingectomy or methotrexate if uncomplicated and small
What are 3 causes of ectopic pregnancy?
- Obstruction (ex. tumors, adhesions, sacrs, infections, clots)
- Reduced endometrial responsiveness (ex. hormone dysregulation, infections, fibroids)
- Embryonic defects
What are 10 absolute contraindications to taking OCPs?
- Thromboembolism
- Pulmonary embolism
- CAD
- CV accident
- Smoker over the age of 35
- Breast/endometrial cancer
- Unexplained vaginal bleeding
- Abnormal liver function
- Severe hypercholesterolemia
- Severe hypertriglyceridemia
What are 10 relative contraindications for OCPs?
- Uterine fibroids
- Lactation
- DM
- SCD
- Hepatic disease
- Hypertension
- Lupus
- Age 40+ with a high risk for vascular disease
- Migraines
- Seizure disorder
What are 4 causes of abortion-induced death?
What is the rate of abortion-induced death?
- Hemorrhage
- Infection
- Thromboembolism
- Anesthetic complications
Rate = 1 in a million
What is a threatened spontaneous abortion?
Any vaginal bleeding before 20 weeks without cervical dilation or fetus expulsion
What causes spontaneous abortion in:
- First trimester
- Second trimester
First trimester:
- Mostly abnormal fetal chromosomes (usually a maternal gametogenesis error)
- Could be infection, immune problem, endocrine problem, maternal anatomic defect
Second trimester:
- Infection
- Maternal uterine/cervical defects (ex. incompetent cervix)
- Maternal systemic disease
- Fetotoxic agents
- Pre-term labour
- What is incompetent cervix?
- Risk factors?
- Presentation?
- Treatment?
- Dilation of the cervix causing exposure of fetal membranes to vaginal flora/trauma
- Surgery, cervical trauma, congenital abnormality
- Infection, discharge, rupture, dilation, short-term cramping/contraction, pressure in vagina, bleeding
- Cerclage, tocolysis, bedrest
Fill in the following chart:
When a pre-natal screening test is positive, what are your options?
- Paying for NIPS (non-invasive pre-natal screening)
- Getting a detailed U/S for soft markers
- Genetic counselling
- Taking a diagnostic test (amniocentesis, CVS)
What is pre-natal screening?
What are 4 methods?
Screening at 11+ weeks of pregnancy for common genetic anueploidies (trisomy 21, 18, and 13)
- Maternal age
- U/S (nuchal translucency, CR length, soft markers)
- Maternal serum screen
- Non-invaisve prenatal screening
- What is nuchal translucency?
- What is a normal value?
- What does an abnormal value indicate?
- When is it performed?
- What is its detection rate
- What is its false positive rate?
- Length of the sonolucent area in the nuchal region of the fetus on U/S
- Normal = 3.0-3.5 or less
- Increased risk of congenital anomalies (cardiac septa/abdominal wall/renal defects, diaphragmatic hernia) or malformation syndromes (NM disorder, skeletal dysplasia, Noonan, Smith-Lemli-Opitz)
- week 11-13
- 75-90%
- 3-9%
What are 6 maternal serum markers?
- PAPP-A = pregnancy associated plasma protein A
- Fee beta-hCG = hCG from placenta
- PIGF = platelet growth factor
- Alpha fetoprotein from baby’s liver (first and second TM types)
- uE3 = unconjugated estriol from baby’s liver and placenta
- DIA = dimeric inhibin-A from placenta
Fill in the following chart with high or low:
- What is non-invasive prenatal screening?
- What does it detect?
- What is its detection rate?
- What is its false positive rate?
- Examining cell-free DNA in the mother’s blood
- Increased DNA from the fetus may indicated trisomy 13/18/21/XXY/XYY
- 99%
- <1%
What is multiple marker screening?
Give 4 examples.
Using multiple methods to create a reasonable risk assessment.
- First trimester screening
- Mid trimester screening
- Integrated pre-natal screening
- Enhanced first trimester screening
Fill in the following chart regarding multiple marker screening examples.
What are soft markers on U/S?
Which may indicate DS?
- Nuchal translucency
- Short femur
- Echogenic intracardiac focus
- Echogenic bowel
- Short/absent nasal bone
- Increased nuchal fold
- Clinodactyly
- Choroid plexus cysts
- Dilated ventricles
DS = nuchal translucency, EICF (LR = 2), increased nuchal fold (LR = 17), echogenic bowel, short/absent nasal bone, clinodactyly
What are 6 separate genetic errors that can result in trisomy 21 (Down Syndrome)?
- Non-disjunction in early meiosis leading to a complete extra copy
- Non-disjunction in early mitosis leading to a mosaic extra copy
- Robetsonian translocations (new or balanced carrier parent)
- Isochromosomes (1 arm duplicated, 1 arm lost)
- Ring chromosomes
- Spontaneous new mutation in the fetus
What are 5 common and visible symptoms of Trisomy 21?
- Transverse palmar flexure
- Gap between first two toes
- Flat facial profile
- Epicanthal folds at eyes
- Short stature (average man = 5ft 1in; average woman = 4ft; 8in)
List 1 common defect in the following organs in those with Down Syndrome.
- Heart
- GI tract
- Blood
- Brain
- Reproductive system
- Atrial septal defects
- Duodenal atresia
- Acute lymphoblastic leukemia
- Risk of Alzheimer’s Disease
- Sterility (males)
Fill in the following chart with different possible presentations of Down Syndrome
What supports are available for management of Down Syndrome? (10)
- Hearing aids
- Tympanostomy tubes
- CPAP machines
- Therapy for speech and language
- Occupational therapy
- Education programs
- Social/Family support
- Medications for behavioural issues, mental illness, and RSV infetion prevention
- Tonsillectomy
- Plastic surgery
What 9 things should those with Down Syndrome be screened for?
- Hearing
- Vision
- T4/TSH levels
- Teeth
- Celiac disease
- Sleep apnea
- Neck X-ray
- ECG/heart U/S
- Testicles
Fill in the following chart concerning appropriate pre-natal vitamin consumption to avoid pathology:
What are 11 “normal” pathological changes in pregnancy?
- Headaches
- Edema
- Nausea/vomiting
- Heartburn
- Constipation
- Fatigue unrelieved by rest
- Leg cramps
- Round Ligament Pain
- Varicose Veins
- Hemorrhoids
- Vaginal Discharge
What is a teratogenic agent?
Any physical (drugs/rads), chemical, or infectious (microbial) agent that, on fetal exposure, can alter fetal morphology (and possibly function)
What are 3 types of structural defects to a fetus?
- Malformation = morpholgoic defect in an organ or body part due to abnormal first TM development
- Deformation = abnormal form/shape/position of a body part due to constraint
- Disruption = defects from interference with a normally developing organ system (after organogenesis usually)
What are the 3 stages of fetal development in regards to teratogenic susceptibility?
- Resistant (all or nothing) = day 0-11
- Maximum susceptibility = day 11-57 (organogenesis)
- Lowered susceptibility = day 57 onward (histogenesis)
What 4 important organs/systems are still susceptible to teratogens after organogenesis (week 9 onward)
- Fetal eyes
- Genitalia
- Hematopoietic system
- CNS
What are the 6 main categories of teratogens?
- Radiation
- Drugs/medications
- Hyperthermia
- Hyperglycemia
- Phenylketonuria
- Infection
Radiation as a teratogen:
- What doses are ok?
- What are sources?
- What are the effects from week 2-4? 4-12? 12-16? 20+?
- 5-10
- Imaging diagnostics, radiation therapy
Week 2-4 = abortion;
Week 4-12 = microcephaly, retardation, cataracts, small eyes
Week 12-16 = retardation
Week 20+ = hair loss, skin lesion, bone marrow suppression
What drug factors determine whether it will have an effect on the fetus? (6)
- Maternal absorption
- Metabolism
- Protein binding/storage
- Molecular size (>1,000 Da don’t easily cross placenta)
- Electrical charge
- Lipid solubility
List 10 common drug teratogens and their common effects
- Alcohol - FAS
- Heroin - neonatal withdrawal
- Phencyclidine - facial abnormalities
- Cocaine - congenital abnormalities, stillbirth, LBW
- Chemotherapy - IUGR, stillbrith, LBW, preterm
- Anti-epileptics (valproic acid, phenytoin, carbamazepine) - NTD
- Lithium - Ebstein’s anomaly
- SSRIs - cardiac septal defects, persistent hypertension
- Benzodiazepines - cleft anomalies
- Warfarin - fetal warfarin syndrome
- ACEI - renal duysfunction, IGUR, oligohydramnios
- Vitamin A derivates (isoretinoin, accutane) - CNS/thymus problems, limb reduction, developmental delay, microagnathia
What are 10 features of the fetal warfarin syndrome?
- Flattened nasal bridge
- Stippled bony epiphyses
- Occular defects
- Extremity hypoplasia
- Developmental retardation
- Seizures
- Scoliosis
- Deafness/hearing loss
- Congenital heart disease
- IGUR
(possible death)
What are 9 features of fetal alcohol syndrome?
- Small head
- Epicanthal folds
- Flat midface
- Smooth philtrum
- Low nasal bridge
- Small eye openings
- Short nose
- Thin upper lip
- Underdeveloped jaw
What 13 infections can be teratogenic? (CHEAPTORCHES)
- Chickenpox/shingles (varicella zoster virus)
- Hepatitis B, C, D, E
- Enteroviruses
- AIDS
- Parovirus B19
- Toxoplasmosis
- Group B Streptococcus
- Listeria
- Candida
- Rubella
- Cytomegalovirus
- Herpes simplex virus
- Syphilis
Rubella virus:
- When does the virus have the most effects?
- What happens in congenital rubella syndrome? (13)
- First month affects 90%, second month affects 22%
- Microcephaly, mental/motor retardation, meningoencephalitis, persistent patent DA, pulmonary artery stenosis, AV septal defects, cataracts, microphthalmia, retinal changes, blindness, sensorineural deafness, IUGR
Varicella Zoster Virus:
- When does the virus have the most effects?
- What happens in congenital varicella? (13)
- First TM affects 2% but severely; Second TM affects 25% but less severely; no effect 28-40 weeks
- Skin scarring/rash, limb hypoplasia, clubfoot, microcephaly, seizures, retardation, autonomic dysfunction, microphthalmia, cataracts, IUGR, fever, pneumonia, death
What are pre-existing risk factors for thromboembolic disease in pregnancy? (4)
- Obesity
- Advanced maternal age
- Previous clots
- Thrombophilic disorders
What are complicated outcomes of thromboembolic disease in pregnancy? (6)
- DVT
- PE
- Hypertensive disorder
- Pre-eclampsia
- SGA infant
- Future recurrent miscarriages
What are treatment options for thromboembolic disease in pregnancy?
- Unfractionated heparin
- Low-molecular-weight heparin (up until week 35)
- Aspiring (up until week 16)
- Warfarin (after pregnancy)
What is antiphospholipid antibody syndrome?
An autoimmune hypercoagulable state caused by antiphospholipid antibodies
What is Asherson syndrome?
APLS leading to rapid organ failure and generalised thrombosis
What 3 proteins are targeted by self-antibodies in APLS?
What are these antibodies?
- Beta-2 glycoproteins –> Lupus anticoagulant antibody
- Annexin 2-5 –> Anti-annexin antibody
- ApoH / cardiolipin –> Anticardiolipin antibody
What are 3 reasons for hypercoagulability in APLS?
- Inhibition of protein C by anti-cardiolipin antibodies binding ApoH
- Inhibition of protein S further decreasing protein C activity
- Inhibition of prothrombin by lupus anticoagulant
What are pregnany related risks of APLS? (6)
- Miscarriage
- Stillbrith
- Pre-term devliery
- Severe pre-eclampsia
- IUGR
- Mental/developmental retardation
What are 4 diagnostic tecniques used in the workup of APLS?
- Prolonged PTT, not correcting on addition of normal plasma
- Liquid phase coagulation assays to check for lupus anticoagulant antibodies
- Solid phase ELISA assay to check for anticardiolipin antibodies
- Genetic screen for underlying thrombophilia
What is required for a clinical diagnosis of APLS? (2)
- Documented episode of arterila/venous/small vessel thrombosis in a deep vein in the absence of inflammation
- 1+ fetal deaths at >10 weeks and/or 3+ fetal deaths at <10 weeks
What are 3 possible ways to diagnose APLS based on lab values?
- Anti-cardiolipin IgG and/or IgM on 2+ occassions less than 8 weeks apart
- Anti-beta2 glycoprotein IgG and/or IgM on 2+ occassions less than 8 weeks apart
- Lupus anticoagulant detected on 2_ occassions less than 8 weeks apart
What are treatment options for APLS?
- Aspirin
- Warfarin (after pregnancy)
- Heparin (during pregnancy)
Postterm Pregnancy
- Define
- List 5 causes
- How is it managed?
- Pregnancy extended beyond 42 weeks’ gestation
- Wrong LMP, anencephaly, congenital primary fetal adrenal hypoplasia, placental sulfatase deficiency, idiopathic
- Expectant until delivery is indicated via the biophysical profile, labour induction when indicated
Biophysical profile
- What factors does it assess?
- Fill out the chart:
- Non-stress test, fetal breathing, fetal tone, fetal motion, quantity of amniotic fluid
What is the diagnostic criteria for each stage of labour to be considered “prolonged” in nulli vs. multiparous women?
How do you manage it in each stage?
Stage 1 latent = >20 hours (N) or >14 hours (M)
- Treat with balloon catheter, amniotomy, oxytocin
Stage 1 active = no change in 4 hours or 5 hours total (N and M)
- Treat with oxytocin and if this fails do a C/S
Stage 2 = >2 hours (N) or >1 hour (M)
- Treat with oxytocin and if this fails do a C/S (negative cm) or forceps/vacuum (positive cm)
Stage 3 = >30 minutes (N and M)
- Uterine massage –> oxytocin –> manual extraction –> D&C surgery
Define placenta accreta, placenta increta, and placenta percreta.
Placenta accreta = chorionic villi attach to myometrium
Placenta increta = chorionic villi invade the myometrium
Placenta percreta = chorionic villi invade the perimetrium (serosa)
Define:
- Pre-term ROM
- Premature ROM
- Pre-term premature ROM
- Prolonged ROM
- ROM before week 37
- ROM during week 37-45 but more than 1 hour before onset of labour
- premature ROM during week 24-37
- Normal ROM, but followed by 18 hours with no labour
Abnormal ROM:
- What are 4 ways to confirm ROM has taken place?
- What is a common cause of abnormal ROM?
- How are abnormal ROM treated? (PPROM, PROM, prolonged)
- What are 2 complications of prolonged ROM?
- Pooling of fluid seen in vagina, nitrazine test (blue), positive fern test, U/S showing olighydramnios
- Group B Strep Infection
- PPROM = deliver if <24 or >34; steroids if 24-34
PROM = induce delivery +/- ampicillin
Prolonged ROM = induce delivery +/- ampicillin
- Chorioamnionitis before delivery; endometritis after delivery
Define:
- Complete placental previa
- Partial placental previa
- Marginal placental previa
- Placenta completely covering cervical os
- Placenta partially covering cervical os
- Placenta ending within 2 cm of cervical os
Placenta previa
- What are 4 risk factors
- What is the presentation?
- What are 3 complications?
- What are 4 possible management steps?
- Twins/triplets, maternal age >35, intrauterine fibroids, maternal smoking
- Intermittent or continuous bleeding after 20 weeks gestation
- Maternal loss of blood, fetal hypoxia, pre-term delivery
- Corticosteroids, bed rest, blood products/IV fluids, C/S
Breech presentation:
- Define
- What are 2 (categories of) causes?
- What are 2 complications?
- How is treated? (2)
- Fetus exiting the birthing canal bottom first and head last
- Inability of fetus to move; insufficient intrauterine space for movement
- Oxygen deprivation; brain/skull injury
- External cephalic version +/- tocolytics, C/S
Cephalopelvic disproportion:
- Define
- List some causes
- How is treated?
- Baby’s head is too large in relation to maternal pelvis, either form large head or small/abnormal shaped pelvis
- Hereditary macrosoma, diabetes, post-term baby, maternal vitamin D deficiency, young maternal age, materanl obstructive tumor
Shoulder dystocia:
- Define
- What are 5 risk factors?
- What are 3 signs?
- What is the treatment?
- Obstructed labour after the delivery of the head due to the anterior shoulder not being able to pass through the pelvis
- Maternal age >35, short mother, small/abnormal maternal pelvis, post-term labour, maternal diabetes
- Turtle sign, erythematous puffy fetal face, failure to deliver shoulders after head
- Leg hyperfelxion, applying pressure, episiotomy, mother getting on all fours, break the baby’s clavicle
Intrauterine hypoxia:
- Define
- What are 4 causes?
- What are 2 complications?
- What is 1 treatment option?
- Deprivation of adequate oxygen to the fetus
- Prolapse/occlusion of umbilical cord, placental infarction, maternal smoking, IUGR
- CNS damage, fetal acidosis
- Hypothermia therapy = lowering baby’s core body temperature
What is the difference between induction and augmentation of labour?
Induction = initiating labour before any spontaneous onset, with the goal of vaginal delivery
Augmentation = enhancing uterine contractiliy when labour has already begun
What is the Bishop score?
What are its components?
What do scores mean?
A cervical scoring system used to determine the potential success of labour induction.
Uses 5 criteria:
- Cervical dilation (cm)
- Cervical effacement (%age)
- Cervical consistency
- Cervical position
- Fetal station
6+ = high likelihood of successful labour
<6 = reduced likelihood of successful labour –> induce cervical ripening
How are values determined in the Bishop score?
What are the absolute indications for inducing labour?
(4 maternal; 4 fetal)
Maternal = pre-eclampsia, DM/CKD/CPD complications
Fetal = chorioamnionitis, post-term, IUGR, isoimmunisation
What are the relative indications for inducing labour?
(4 maternal; 4 fetal; 1 uteroplacental)
Maternal = chronic/gestational HT, gestational DM, history of rapid labour, far from a hospital
Fetal = Premature ROM, macrosomia, demise, major anomaly
Uteroplacental = unexplained oligohydramnios
What are the absolute contra-indications for inducing labour?
(2 maternal; 3 fetal; 4 uteroplacental)
Maternal = active genital herpes, serious chronic medical condition
Fetal = mal-presentation, no fetal head flexion, fetal distress
Uteroplacental = cord prolapse, placenta previa, vasa previa, prior C/S
What are the relative contra-indications for inducing labour?
(2 maternal; 1 fetal; 4 uteroplacental)
Maternal = cervical carcinoma, pelvic deformities
Fetal = extremely large
Uteroplacental = low-lying placenta, unexplained vaginal bleeding, cord presentation, myomectomy
What are 4 ways to ripen a cervix?
- Hormones (prostaglandins, oxytocin, estrogen, mifepristone, relaxin)
- Amniotomy
- Membrane stripping
- Mechanical dilation (hygroscopic dilation, balloon catheter)
What are 2 ways to induce labour?
- Hormones (oxytocin, prostaglandin, mifepristone)
- Amniotomy
What are 3 risks involved in inducing labour?
- Hypoxia –> oxytocin and prostaglandin may cause abnormal/excessive contractions which diminish baby’s oxygen supply
- Infection from ROM
- Post-partum hemorrhage –> induction may increase uterine muscle exhaustion or exogenous hormones may prevent uterine contraction around spiral arteries
What do the following indicate:
- Type I deceleration of FHR
- Type II/delayed deceleration of FHR
- Variable FHR
- Nothing to worry about
- Hypoxia
- Compression of umbilical cord
