Marjorie has evidence of developing shock.  She has many risk factors for this such as a high temperature, possible dehydration from the history and the presence of bacteria on microscopy of the urine suggesting infection.

Causes of shock (also covered in the meningitis scenario)

• Reduced cardiac output (CO):

• Hypovolaemic shock

• Haemorrhage

• External, including gastrointestinal

• Internal (Chest; abdomen; pelvis; retroperitoneum; long bones)

• Vomiting

• Diarrhoea

• Diuresis

• Burns

• Cardiogenic shock

• Myocardial infarction

• Myocardial contusion

• Myocarditis

• Cardiac arrhythmia

• Negatively inotropic drug overdose (e.g. beta blockers or calcium channel blockers)

• Obstructive shock

• Tension pneumothorax

• Massive PE

• Cardiac tamponade

• Reduced systemic vascular resistance (SVR):

• Septic shock

• Anaphylactic shock

• Neurogenic shock

Pathophysiology of shock

• Blood pressure (BP) is related to cardiac output (CO) and systemic vascular resistance (SVR) by the following equation:

• BP = CO x SVR

• CO is the volume of blood pumped by the heart per minute and is in turn related to heart rate (HR) and stroke volume (SV) as follows:

• CO = HR x SV

• SV is the volume of blood pumped by the heart per contraction and is determined by

• Preload

• Myocardial contractility

• Afterload

• Preload is the ventricular wall tension at the end of diastole and reflects the degree of myocardial muscle fibre stretch; it is determined by volume status, venous capacitance and the difference between mean venous pressure and right atrial pressure

• Preload is related to SV by the Frank-Starling mechanism; increased fibre length initially leads to an increased SV but above a certain point, the fibres become overstretched and further filling results in a decreased SV, as is the case in cardiac failure

The pathophysiological mechanisms that lead to shock secondary to sepsis (also covered in the meningitis scenario)

Bacterial cell wall components (endotoxin (lipopolysaccharide), peptidoglycan, muramyl dipeptide, and lipoteichoic acid) and bacterial products (staphylococcal enterotoxin B, toxic shock syndrome toxin-1, Pseudomonas exotoxin A, and M protein of hemolytic group A streptococci) may contribute to the progression of a local infection to sepsis. E. coli is the most common bacterium associated with uniary tract infection and is a gram negative bacteria that releases lipopolysaccharide into the circulation during septicaemia. Hypotension due to diffuse vasodilation is the most severe expression of circulatory dysfunction in sepsis. It is probably an unintended consequence of the release of vasoactive mediators, whose purpose is to improve metabolic autoregulation (the process that matches oxygen availability to changing tissue oxygen needs) by inducing appropriate vasodilation. Mediators include the vasodilators prostacyclin and nitric oxide (NO), which are produced by endothelial cells.

In the central circulation (i.e., heart and large vessels), decreased systolic and diastolic ventricular performance due to the release of myocardial depressant substances is an early manifestation of sepsis. Despite this, ventricular function may still be able to use the Frank Starling mechanism to increase cardiac output, which is necessary to maintain the blood pressure in the presence of systemic vasodilation. Patients with pre-existing cardiac disease (e.g., elderly patients) are often unable to increase their cardiac output appropriately.

In the regional circulation (i.e., small vessels leading to and within the organs), vascular hyporesponsiveness (i.e., inability to appropriately vasoconstrict) leads to an inability to appropriately distribute systemic blood flow among organ systems. As an example, sepsis interferes with the redistribution of blood flow from the splanchnic organs to the core organs (heart and brain) when oxygen delivery is depressed.

The microcirculation (i.e., capillaries) may be the most important target in sepsis. Sepsis is associated with a decrease in the number of functional capillaries, which causes an inability to extract oxygen maximally. Compared to normal controls or critically ill patients without sepsis, patients with severe sepsis have decreased capillary density. This may be due to extrinsic compression of the capillaries by tissue oedema, endothelial swelling, and/or plugging of the capillary lumen by leukocytes or red blood cells (which lose their normal deformability properties in sepsis).

At the level of the endothelium, sepsis induces phenotypic changes to endothelial cells. This occurs through direct and indirect interactions between the endothelial cells and components of the bacterial wall. These phenotypic changes may cause endothelial dysfunction, which is associated with coagulation abnormalities, decreased red blood cell deformability, upregulation of adhesion molecules, adherence of platelets and leukocytes, and degradation of the glycocalyx structure. Diffuse endothelial activation leads to widespread tissue oedema.

The urine dipstick provides a rapid semiquantitative assessment of urinary characteristics on a series of test pads embedded on a reagent strip. Most dipsticks permit the analysis of the following core urine parameters: heme, leukocyte esterase, nitrite, albumin, hydrogen ions, specific gravity, and glucose. Dipsticks from different manufacturers vary as to the other urine parameters that are analyzed. 

Detection of heme
Heme acts as a pseudoperoxidase, and when heme-containing urine is exposed to peroxide and a chromogen on the test pad, a colour change takes place. However, a positive dipstick for heme may result not only from urinary red blood cells (RBCs), but also from free hemoglobin or free myoglobin. In addition, the dipstick may be falsely positive if there is semen present in the urine. Thus, a positive dipstick does not establish the presence of RBCs in the urine, and the diagnosis of hematuria requires confirmation with microscopy.

Detection of leukocyte esterase
Leukocyte esterase released by lysed neutrophils and macrophages is a marker for the presence of white blood cells (WBCs). Excessively dilute urine may favor cell lysis and lower the threshold for test positivity. By contrast, a concentrated urine may impede cell lysis and therefore produce a false-negative result. Proteinuria and glucosuria may also lead to a false-negative test for leukocyte esterase

Nitrite
Many enterobacteriaceae species, the most common microorganisms causing urinary tract infections, elaborate the enzyme nitrate reductase, which confers the ability to convert urinary nitrate to nitrite. Thus, nitrite-positive urine may indicate underlying bacteriuria. However, bacteriuria or frank infection may still be present in the absence of nitrite positivity. This would occur with organisms expressing low levels of nitrate reductase (eg, enterococcus), or when urine dwell time in the bladder is short

Protein
The urine dipstick test for protein is most sensitive to albumin and provides a semiquantitative means of assessing albuminuria. Albumin in the urine is not normal and can indicate the presence of a number of diseases affecting the glomerulus.

Hydrogen ion concentration
The urine hydrogen ion concentration, measured as the pH, reflects the degree of acidification of the urine. The urine pH ranges from 4.5 to 8, depending upon the systemic acid-base balance.

Microscopy

Red blood cells in the urine (Hematuria) may be grossly visible or microscopic. Microscopic hematuria is commonly defined as the presence of two or more RBCs per high-powered field in a spun urine sediment. The urine colour change in gross hematuria does not necessarily reflect a large degree of blood loss, since as little as 1 mL of blood per litre of urine can induce a visible colour change. Haematuria can be transitory or persistent and has many causes. One cause of transient haematuria is urinary tract infection. This is typically accompanied by pyuria (white blood cells in the urine) and bacteriuria (bacteria in the urine). Bacteria are often seen in the urine, although the clinical significance of bacteriuria is generally guided by patient symptoms.