• Autosomal Dominant Polycystic Kidney Disease
  • Type 1: ~85%, average age of developing ESRD is around 50yo
  • Type 2: ~15%, average age of developing ESRD is around 70yo
• Cardiovascular disease is the most common cause of death in ADPKD and ADPKD is the most common inherited kidney disease
• For an infected renal cyst, use a lipophilic antibiotic (for good cyst penetration) such as quinolones or bactrim
• ADPKD is present in 5-10% of dialysis patients in the US
• Renal manifestations include recurrent UTIs, cyst infection, hematuria from cyst hemorrhage, and nephrolithiasis (usually uric acid stones)
• Extra-renal manifestations of ADPKD include diverticulosis, abdominal hernias, cysts in liver/thyroid/pancreas/seminal vesicles/etc, mitral valve prolapse, and cerebral aneurysms.
• The biggest risk factor for cerebral aneurysms in patients with ADPKD is a family member with cerebral aneurysms
• DDAVP for uremic platelets works by increasing vwF from endothelial cells

• Diagnostic Criteria for APLS: Need ONE lab criteria (confirmed 12 weeks apart) and ONE clinical criteria.
  • LAB Criteria: B2 Glycoprotein, Anti-Cardiolipin antibody, or lupus anticoagulant (as measured by prolonged DRVVT which does not correct with a mixing study)
  • CLINICAL Criteria: Any Thrombosis (venous/arterial) OR fetal loss/miscarriage
• APLS can be a primary disorder or secondary to other disease (usually Lupus)
• Clinical Features of APLS: 50% have prolonged PTT, 20% with livedo reticularis, cardiac valvular disease (MR), 32% DVT, 13% stroke, 7% hemolytic anemia
• Massive PE refers to PE causing hemodynamic instability (SBP < 90) while submassive PE refers to PE causing right heart strain without hypotension
• Right heart strain from PE: Look for signs of right ventricular hypertrophy and dilatation on EKG, Echo. McConnell’s sign on ECHO is RV hypokinesis with apical sparing

Teaching Pearls:

• Average Age 30-55 years old; F:M ratio 3:1
• Symmetric polyarthritis
• Morning stiffness >1 hour that improves with activity
  • OA worsens with activity
• Joint Involvement:
  • Almost always involves MCP, PIP, wrist, MTP
  • Spares the DIP and lumbar spine
    • Think of OA with DIP involvement
  • Can occasionally affect large joints
  • Swan Neck Deformity
  • Boutonniere deformity
  • Ulnar Deviation
  • C1-C2 subluxation (Atlanto-axial instability)
    • This specifically can also be seen in Downs syndrome
  • Peri-articular osteopenia
• RA is an independent risk factor for pre-mature coronary artery disease
• RA + pancytopenia + splenomegaly = Felty Syndrome
• RA is a systemic disease that can affect multiple organs. Can be a cause for secondary amyloidosis.
• Amyloidosis – deposition disease that clinically affects the kidneys, liver, and heart.
  • Kidney – can lead to nephrotic syndrome
  • Hepatomegaly
  • Restrictive cardiomyopathy
  • Thickening of tongue – lateral scalloping seen on exam
  • Waxy skin
  • Coagulopathy – amyloid protein causes binding to factor X
  • Neuropathy
  • GI – causing a malabsorptive syndrome
• Diagnosis requires abdominal fat pad biopsy with Congo red stain to check for apple-green birefringence.

Teaching Pearls:

• Clinical Features of CREST syndrome
  • Calcinosis of soft tissue, Raynauds phenomenon, Esophageal dysmotility, Sclerodactyl, Telangiectasia
• Diffuse Cutaneous Systemic Sclerosis (dcSS)
  • Skin Findings – Extends past elbows and knees from hands and feet, respectively. Can be seen along torso and face/neck
  • Antibody – anti-Scl-70
  • Pulm manifestation – interstitial lung disease
  • Associated with sclerodermal renal crisis
  • Not associated with CREST
• Limited Cutaneous Systemic Sclerosis (lcSS)
  • Skin Findings – hands/feet, distal to elbows and knees. Face and neck
  • Antibody – ANA centromere pattern
  • Pulm manifestation – pulmonary hypertension
  • Not associated with sclerodermal renal crisis
  • Associated with CREST
• Dermatomyositis
  • Heliotropic rash, shawls and V sign, gottron’s papules. Mechanic hands
  • Classically associated with proximal muscle weakness
  • Elevated CK and aldolase.
  • Other studies to consider: EMG and muscle biopsy (definitive diagnosis)
  • Associated with anti-Jo-1 antibody (anti-synthetase syndrome)
    • Higher association with ILD and worse prognosis
  • Higher association with malignancy.
    • Colon, breast, ovarian, prostate, etc.
  • Few case reports have found an association with oropharyngeal dysphagia, and seems to suggest a poor prognosis sign.
• Serologic Studies/Associations
  • Anti-centromere pattern of ANA – lcSS
  • Anti-dsDNA Ab – SLE
  • Anti-smooth muscle Ab – autoimmune hepatitis
  • Anti-La/SSB antibody – Sjogrens, neonatal SLE
  • Anti-RNP antibody – Mixed connective tissue disease
  • Antihistone antibody – drug induced lupus
  • Anti-Scl-70 Ab – dcSS
  • Anti-Ro/SSA antibody – Sjogrens, neonatal heart block
  • c-ANCA – Wegeners granulomatosis
  • p-ANCA – Churg Strauss, microscopic polyangitis
  • Anti-Jo-1 Ab – dermatomyositis/polymyositis/anti-synthetase syndrome
  • Anti-CCP Ab – Rheumatoid arthritis

Teaching Pearls:

• Can be categorized into the following:
  • Hyperosmolar
    • Hyperglycemia, mannitol use
  • Iso-osmolar
    • Hypertriglyceridemia, hyperparaproteinemia
  • Hypo-osmolar
• Hypo-osmolar hyponatremia can be divided into different categories based on volume status:
  • Hypovolemic
    • GI losses, diuretic use, blood loss
    • ↓↓salt/↓H2O
    • Urine osm >100mOsm/L
    • Urine Na <20 mmol/L
  • Euvolemic
    • siADH, psychogenic polydipsia, adrenal insufficiency, hypothyroidism, low solute intake (tea toast diet or beer potomania)
    • Salt/↑H2O
    • siADH
      • Urine osm >100mOsm/L
      • Urine Na >40 mmol/L
    • Psychogenic polydipsia
      • Urine osm<100mOsm/L
      • Urine Na >20mmol/L
  • Hypervolemic
    • CHF, nephrotic syndrome, cirrhosis
    • ↑Salt/↑↑H2O
    • Urine osm >100mOsm/L
    • Urine Na <20mmol/L
• Hypothyroidism presents as a hypoosmolar euvolemic hyponatremia.
  • Can present with a clinical picture and urine studies similar to siADH
  • Can also present as a picture of CHF.
    • Often these patients have myxedema coma.
    • Theorized that the decreased cardiac output leads to decreased glomerular filtration, leading to poor excretion of free water.
• Adrenal insufficiency commonly presents with hyponatremia, hyperkalemia, and metabolic acidosis.
• Low solute diet (tea toast diet and/or beer potomania)
  • Kidneys can dilute urine to as low as 50mOsm/L.
  • If intake of solute is very low, then it limits the amount of free water that can be excreted.
• For more teaching points, check out the hyponatremia section on http://www.professorebm.com.

Teaching Pearls:

• Esophageal varices are seen in roughly 50% of patients with cirrhosis.
• About 33% of patients with cirrhosis and esophageal varices will have at least one clinical presentation of esophageal variceal (EV) bleeding.
• Mortality of 15-20% associated with each episode of esophageal bleeding event.
• EV bleeding comprises of 33% of all cirrhosis-related deaths.
• Risk of EV bleeding correlates with size of varices and other characteristics such as nipple sign and red wales sign.
• Pre-primary prophylaxis – Management of cirrhotic patients without esophageal varices
  • Management focuses on treating the underlying cause of cirrhosis.
  • Screening occurs ~2-3 years.
• Primary Prophylaxis – Management of cirrhotic patients with EV but no clinical history of GI bleed.
  • Medical management with beta blockers
    • Performed in those with medium-large varices, or small varices with red wales/nipple sign.
  • Esophageal band ligation
    • Performed in those with large varices
  • Continued Monitoring
    • Those with small EV without red wales/nipple sign.
• Immediate interventions to consider in patients with suspected EV bleeding:
  • At least 2 large bore PIVs (16 or 18G) or central line
  • Fluid resuscitation
  • Type and screen blood
  • Monitor hemodynamics
  • Start protonix (bolus and gtt) and octreotide (bolus and gtt)
  • Start ceftriaxone for SBP prophylaxis
• Pantoprazole
  • PPI will increase the pH of the gastric lumen to 5-6 from 1-2.
  • pH changes help with improving clot formation
• Octreotide
  • Works by inhibiting endogenous substances – leads to splanchnic vasoconstriction, decreasing portal flow, leading to decreased portal pressures.
• SBP Prophylaxis Conditions
  • History of SBP
  • Cirrhosis with GI bleed
  • Ascitic TP <1
• Management of gastric varices differ from esophageal varices.
  • Cyanoacrylate injection and/or TIPS

Teaching Pearls:

• FEV1/FVC Ratio <0.7 suggestive of obstructive parenchymal disease
• DLCO – ability for gas to diffuse across alveolar capillary membrane.  CO (inhaled) – CO (exhaled). CO has a high affinity for Hb. If CO (exhaled) is higher than expected, DLCO is low and this is suggestive of diffusion problem.
  • False Positive
    • Anemia
    • Pulmonary hypertension
  • False Negative
    • Pulmonary hemorrhage
• Pulmonary Function Tests
  

  	FEV1	FVC	FEV1/FVC	DLCO	TLC	RV	F-V
  Emphysema	Decrease	Decrease/No change	<70%	Decrease	Normal/increase	Normal/increase	C
  Chronic Bronchitis	Decrease	Decrease/No change	<70%	Normal	Normal/increase	Normal/increase	C
  ILD	Normal/Decrease	Normal/Decrease	Normal/Increase	Decrease	Decrease	Decrease	A
  Tracheal stenosis	Decrease	Decrease/normal	Decrease	Normal	Normal	Normal	B
  Resp muscle weakness	Decrease	Decrease	Normal	Normal	Decrease	Increase	D

  A.  

  B.

• C.
• D.

Teaching Pearls: 

• ANA negative lupus, check SSA/SSB which are associated with neonatal lupus and congenital heart block
• ANA positive in 99% of patients with lupus, but low specificity
• double stranded DNA antibodies are used to monitor disease severity in lupus
• check C3, C4, and double stranded DNA to work up possible lupus flare
• Drug induced lupus: Look for positive ANA and anti-histone antibodies. Also look for exposure to procainamide, hydralazine, chlorpromazine, PTU, phenytoin, minocycline, and TNF inhibitors.

• Pathophysiology of T4 secretion: TSH secreted in the anterior pituitary and stimulates the TSH receptor in the thyroid to secrete thyroid hormone
• Clinical presentation of Hyperthyroidism: Hyperdefecation (not diarrhea), osteoporosis, oligomenorrhea in pre-menopausal females, hair changes, palpitations, arrhythmias
• Etiologies of hyperthyroidism
  • Grave’s Disease (most common cause of hyperthyroidism)
  • Destructive thyroiditis (subacute, silent, postpartum)
  • Multinodular Goiter/Toxic Adenoma
  • Medication-induced (amiodarone, lithium, IFN-a, etc)
  • Factitious
• Antibodies
  • Anti-TPO and anti-thyroglobulin Ab seen with Hashimoto’s Disease (hypothyroidism)
  • TSI (thyroid stimulating immunoglobulin) and TBII associated with Graves Disease.
    • TSI binds to TSH receptors on thyroid gland, stimulating production of thyroid hormone.
    • TSI also binds to TSH receptors located on fibroblasts, stimulating proliferation and glycosaminoglycan production in retro-orbital space.
• Clinical Presentation specific to Graves include pretibial myxedema (5% patients with Graves), exophthalmos (25% of patients with Graves)
• Work-up of Hyperthyroidism
  • If evidence for Graves Disease, then GD likely diagnosis.
  • Evidence of nodules on physical Exam:
    • If None: Perform RAI uptake scan and antibody studies.
      • If increased uptake, elevated thyroid hormone due to over-synthesis
        • If diffuse uptake, think Graves Disease
        • If patchy uptake, think toxic multinodular goiter
      • If decreased uptake, think of factitious or destructive causes (subacute, silent, postpartum.
    • If Present: Get RAIU scan and thyroid ultrasound to distinguish TNG vs TA and/or evidence of cold nodules. Check for any concerning factors for thyroid cancer.
  • Thyroglobulin: Precursor to thyroid hormone production. Combined with iodine to produce T4.
    • May be used to differentiate factitious vs destructive thyroiditis, surveillance for thyroid cancer.
• Treatment Options:
  • Thionamides – Methimazole versus PTU
    • Watch for drug rash and/or agranulocytosis
  • Radioactive iodine ablation
    • Do not use in patients with Graves Disease with severe ophthalmopathy as this can worsen symptoms.
  • Surgery

Teaching Pearls

• Duration of Diarrhea
  • Acute < 14 days
  • Chronic >4 weeks
• Types of Diarrhea
  • Secretory
    • Stool osmole gap <50
  • Osmotic
    • Stool osmole gap >100
  • Inflammatory
    • Evidence of blood and/or mucoid stools
  • Malabsorption
    • Protein-losing enteropathy
    • CHO malabsorption
    • Fat malabsorption
• Bacterial Causes of Blood Diarrhea
  

  	Source	Presentation	Complications	Treatment
  STEC (EHEC)	Uncooked hamburger meat. Fecal-oral route	Abd pain with bloody diarrhea +/- fever	HUS	No antibiotics indicated; supportive care
  Shigella	Shellfish, fecal oral route	Dysentery (bloody mucoid stools), tenesmus, fever, abdominal pain	Reiters Disease	Flouroquinolone; 3rd generation cephalosporin
  Salmonella	Undercooked raw eggs, chicken, fruits	Fever, abdominal pain, occult/overt bleeding	Bacteremia, aortitis, osteomyelitis in those with sickle cell disease	Only treat when symptoms are severe
  Campylobacter	Poultry	Occult bleeding	Reiters disease, Guillain-Barre Syndrome	Treat only if severe with macrolides