The mechanism is thought to be that, following the initiation of warfarin, both protein C antigen and activity levels drop rapidly, compared with levels of other vitamin K-dependent factors such as factors IX and X, and prothrombin. This observed rapid early fall in protein C level prompted the hypothesis that the administration of warfarin to protein C-deficient individuals causes a temporary exaggeration of the imbalance between pro- coagulant and anticoagulant pathways; that is, the early suppressive action of warfarin on protein C may not be counterbalanced by the anticoagulant effect created by the decline in other vitamin K-dependent factors, thereby leading to a relative hypercoagulable state at the start of treatment. This leads to thrombotic occlusions of the microvasculature with resulting necrosis.
Warfarin induced skin necrosis
Exophthalmos
The
etiological basis of proptosis can include inflammatory, vascular, infectious,
cystic, neoplastic (both benign and malignant, metastatic disease), and
traumatic factors. Some examples include infectious causations such as orbital
cellulitis and subperiosteal abscesses. Traumatic causations could be orbital
emphysema, retro-orbital hemorrhage, and carotid-cavernous fistula. Vascular
causations not traumatically related would be orbital arteriovenous
malformation (AVM) varices and aneurysms. Neoplastic causations include
adenocarcinoma of the lacrimal gland, pleomorphic adenoma of the lacrimal
gland, meningioma, lymphoma, and metastatic disease.
A
ruptured lymphangioma can enlarge after its rupture and sequestering of heme,
which pathologically is described as a chocolate cyst. Orbital varices can
result in proptosis with increased venous pressure in the orbit, as seen with a
Valsalva maneuver or change in postural position.
Bladder outlet obstruction (BOO)
Functional obstruction may be caused by detrusor-sphincter dyssynergia (DSD), either at the level of the smooth muscle or rhabdosphincter; primary bladder neck obstruction, which may be functional and anatomic in character; or due to dysfunctional voiding, associated with learned voiding disorders or pelvic floor dysfunction associated with pain syndromes.
Anatomic obstruction in men results most commonly from benign prostatic enlargement (BPH) or urethral stricture.
Examination of historical and physical evidence of both onset and magnitude and severity of symptoms is critical in the primary evaluation of these patients. In men, benign prostatic obstruction (BPO) is the most common cause of BOO and stems from a variety of etiologies. Other causes of BOO include urethral stricture disease, dysfunctional voiding, neurogenic-based detrusor-sphincter dyssynergia (DSD), and primary bladder neck obstruction.
A
normal flow rate in men does not preclude the possibility of obstruction.
Concomitant analysis of flow rates and residual volumes is important to avoid
misinterpretation of isolated data. Urodynamics, alternative radiologic
procedures, or cystoscopy is recommended in the case of failed presumptive
therapy, a complex presentation scenario, or when a diagnosis is in doubt. Formal
urodynamic evaluation is usually reserved for complicated cases and is often
performed in conjunction with a pressure flow evaluation.
Clinical Hematology
- Old samples cause RBCs to swell, thus increasing PCV and MCV and decreasing MCHC.
- Lipemia causes a falsely high Hgb reading, and hence a falsely high MCHC.
- Hemolysis causes PCV to decrease while Hgb remains unchanged, again leading to a falsely high MCHC
- Underfilling of the tube causes RBCs to shrink, causing PCV and MCV to decrease and MCHC to increase.
- Autoagglutination causes a falsely low RBC count, and hence a falsely high MCV.
Hip fracture
A
hip fracture is one of the most serious consequences of falls in the elderly,
with a mortality of 10% at one month and 30% at one year.
There
is also significant morbidity associated with hip fractures, with only 50%
returning to their previous level of mobility and 10 to 20% of patients being
discharged to a residential or nursing care placement.
Up
to 20% of patients with hip fractures will develop a postoperative complication,
with chest infections (9%) and heart failure (5%) being the most common.
Developing
heart failure following a hip fracture has a very poor prognosis, with a one-year
mortality of 92% and a 30-day mortality of 65%.
For
chest infections, the one-year mortality is 71% and 43% within 30 days.
The
effect of timing of surgical intervention on mortality remains a controversial
topic. Various studies have demonstrated an improvement in mortality following
early surgical intervention, but other studies did not. However, there is
widespread evidence that early operative intervention does improve outcomes,
including morbidity (especially infections), pressure sores, pain, and length
of stay.
Circle of Willis
The
Circle of Willis is an arterial polygon (heptagon) formed as the internal
carotid and vertebral systems anastomose around the optic chiasm and
infundibulum of the pituitary stalk in the suprasellar cistern. This
communicating pathway allows equalization of blood-flow between the two sides
of the brain, and permits anastomotic circulation, should a part of the
circulation be occluded.
A complete circle of Willis (in which no component is absent or hypoplastic) is only seen in 20-25% of individuals. Posterior circulation anomalies are more common than anterior circulation variants and are seen in nearly 50% of anatomical specimens.
Hemochromatosis
Hemochromatosis is a disorder associated with deposits
of excess iron that causes multiple organ dysfunction. Hemochromatosis has been
called “bronze diabetes” due to the discoloration of the skin and associated
disease of the pancreas. Hereditary hemochromatosis is the most common
autosomal recessive disorder in whites. Secondary hemochromatosis occurs
because of erythropoiesis disorders and treatment of the diseases with blood
transfusions.
A common initial presentation is an asymptomatic
patient with mildly elevated liver enzymes who is subsequently found to have
elevated serum ferritin and transferrin saturation. Ferritin levels greater
than 300 ng per mL for men and 200 ng per mL for women and transferrin
saturations greater than 45% are highly suggestive of hereditary
hemochromatosis.
Phlebotomy is the mainstay of treatment and can help
improve heart function, reduce abnormal skin pigmentation, and lessen the risk
of liver complications. Liver transplantation may be considered in select
patients. Individuals with hereditary hemochromatosis have an increased risk of
hepatocellular carcinoma and colorectal and breast cancers. Genetic testing for
the hereditary hemochromatosis genes should be offered after 18 years of age to
first-degree relatives of patients with the condition.
Brain natriuretic peptide
Brain natriuretic peptide
BNP is initially synthesized as a 134–amino-acid
peptide called pre-pro BNP. The secondary cleaving of a 26–amino-acid signal
peptide results in the formation of pro-BNP or BNP 1-108. This molecule is
cleaved by furin, an endo-protease, into BNP 32 and N-terminal BNP (NT-BNP
1-76).
Major points to remember regarding BNP and NT-proBNP include:
- A major application of both BNP and proBNP testing is the evaluation of patients with congestive heart failure. If heart failure responds to therapy, concentrations of BNP and NT-proBNP should decline, indicating progress of therapy. If a patient does not respond, values may be increased gradually.
- In general, NT-proBNP is more stable (up to seven days at room temperature and up to four months if stored at −20°C) than BNP, which is not stable for a day even if the specimen is stored in a refrigerator. Therefore, BNP analysis must be performed as soon as possible after collecting the specimen.
- The cut-off level of BNP and NT-proBNP depends on age, as values tend to increase with advancing age. In general, heart failure is unlikely if the BNP value is less than 100 pg/mL and heart failure is very likely if the value is over 500 pg/mL. For NT-proBNP, the normal value for a person 50 years or younger is usually 125 ng/mL, but heart failure is unlikely if the NT-proBNP value is<300 pg/mL. However, heart failure is likely if the value is>450 pg/mL (>900 pg/mL in a patient of age 50 and above).
- Patients with end-stage renal disease and dialysis patients usually show higher BNP and NT-proBNP in serum than normal individuals.
Malnutrition
Malnutrition is an imbalance between the nutrients your body needs to function and the nutrients it gets. It is an independent risk factor that negatively influences patients’ clinical outcomes, quality of life, body function, and autonomy. Early identification of patients at risk of malnutrition or who are malnourished is crucial in order to start a timely and adequate nutritional support. Nutrition support refers to enteral or parenteral provision of calories, protein, electrolytes, vitamins, minerals, trace elements, and fluids.
Historically, serum proteins such as albumin and prealbumin (i.e. transthyretin) have been widely used by physicians to determine patients’ nutritional status. Other markers that have been studied include retinol-binding protein (RBP), transferrin, total cholesterol and indicators of inflammation such as C-reactive protein (CRP) and total lymphocyte count (TLC).
Aortic valve stenosis
Among
symptomatic patients with medically treated moderate-to-severe aortic stenosis,
mortality from the onset of symptoms is approximately 25% at 1 year and 50% at
2 years. Symptoms of aortic stenosis usually develop gradually after an
asymptomatic latent period of 10-20 years.
Systolic
hypertension can coexist with aortic stenosis. The carotid arterial pulse
typically has a delayed and plateaued peak, decreased amplitude, and gradual
downslope (pulsus parvus et tardus).
Other
symptoms of aortic stenosis include the following:
- Pulsus alternans: Can occur in the presence of left ventricular systolic dysfunction
- Hyperdynamic left ventricle: Unusual; suggests concomitant aortic regurgitation or mitral regurgitation
- Soft or normal S1
- Diminished or absent A2: The presence of a normal or accentuated A2 speaks against the existence of severe aortic stenosis
- Paradoxical splitting of the S2: Resulting from late closure of the aortic valve with delayed A2
- Accentuated P2: In the presence of secondary pulmonary hypertension
- Ejection click: Common in children and young adults with congenital aortic stenosis and mobile valve leaflets
- Prominent S4: Resulting from forceful atrial contraction into a hypertrophied left ventricle
- Systolic
murmur: The classic crescendo-decrescendo systolic murmur of aortic stenosis
begins shortly after the first heart sound; the intensity increases toward mid
systole and then decreases, with the murmur ending just before the second heart
sound.
Lasix (Furosemide)
- Inhibits the reabsorption of sodium and chloride from the loop of Henle and distal renal tubule.
- Increases renal excretion of water, sodium, chloride, magnesium, potassium, and calcium.
- Effectiveness persists in impaired renal function.
- Absorption: 60–67% absorbed after oral administration (↓ in acute HF and in renal failure); also absorbed from IM sites; IV administration results in complete availability; 99.6% absorbed after SUBQ administration.
- Protein Binding: 91–99%.
- Metabolism and Excretion: Minimally metabolized by liver, some non-hepatic metabolism, some renal excretion as unchanged drug.
- Half-life: 30–120 min (↑ in renal impairment).