Mark Nelligan (1)

Mark Nelligan (1)

1. Summary

   • 39 year old male, presented to the GP with feeling unwell for six or seven months. He has noticed ankle swelling, feels increasingly tired and weak, has bouts of nausea during the day, feels itchy all over and has to urinate frequently at night. No significant PMH or MH
   • On examination, he has pitting oedema upto his mid shins, hypertension, a slightly raised temp, JVP of 6cm and pale conjunctivae
   • You perform a urine analysis: Glucose negative, protein +++, blood ++. Bloods are done and show high urea and creatinine, low eGFR, Hb, bicarbonate and albumin
     • His ECG shows Rate - 75 beats/min. Rhythm – sinus, regular. Axis - left axis deviation evident from positive R wave in lead I and negative R wave in lead II. Left ventricular hypertrophy evident from leads V5 (R wave = 2.7 cm) and V6 (R wave = 2.5 cm).
   • He is refered to the renal outreach clinic and on arrival he has bilateral coarse basal crepitations
   • HIs kidney US showns bilaterally small kidneys with increased echogenicity and an echo is also done. His CXR shows pulmonary oedema
   • Repeat bloods are done and he has high urea, creatinine and phosphate and low eGRF, albumin and calcium
   • Dr Wilson decides to admit Mark to the renal ward. On the ward round he explains to Mark that his kidney function has declined considerably.
   • It is decided that he does not need any calcium supplementation or a renal biopsy
     • Further blood tests for blood group, plasma parathormone (PTH), HIV, serum immunoelectrophoresis, hepatitis B surface antigen, hep B core Ab, hep C Ab, hep C RNA and urinary Bence Jones proteins are all normal

2. The Anatomy of the Kidney

   • The kidneys lie retroperitoneally (behind the peritoneum) in the abdomen, either side of the vertebral column. They typically extend from T12 to L3, although the right kidney is often situated slightly lower due to the presence of the liver. Each kidney is approximately three vertebrae in length.
   • The kidneys are encased in complex layers of fascia and fat. They are arranged as follows (deep to superficial)
     • Renal capsule – tough fibrous capsule. Perirenal fat – collection of extraperitoneal fat. Renal fascia (also known as Gerota’s fascia or perirenal fascia) – encloses the kidneys and the suprarenal glands. Pararenal fat – mainly located on the posterolateral aspect of the kidney.
   • The renal parenchyma can be divided into two main areas – the outer cortex and inner medulla. The cortex extends into the medulla, dividing it into triangular shapes – these are known as renal pyramids. The apex of a renal pyramid is called a renal papilla.
     • Each renal papilla is associated with a structure known as the minor calyx, which collects urine from the pyramids. Several minor calices merge to form a major calyx. Urine passes through the major calices into the renal pelvis, a flattened and funnel-shaped structure. From the renal pelvis, urine drains into the ureter, which transports it to the bladder for storage.
   • The kidneys are supplied with blood via the renal arteries, which arise directly from the abdominal aorta, immediately distal to the origin of the superior mesenteric artery. Due to the anatomical position of the abdominal aorta (slightly to the left of the midline), the right renal artery is longer, and crosses the vena cava posteriorly.
     • The renal artery enters the kidney via the renal hilum. At the hilum level, the renal artery forms an anterior and a posterior division, which carry 75% and 25% of the blood supply to the kidney, respectively. Five segmental arteries originate from these two divisions.
   • The kidneys are drained of venous blood by the left and right renal veins. They leave the renal hilum anteriorly to the renal arteries, and empty directly into the inferior vena cava. As the vena cava lies slightly to the right, the left renal vein is longer, and travels anteriorly to the abdominal aorta below the origin of the superior mesenteric artery. The right renal artery lies posterior to the inferior vena cava.

3. Causes of his Blood Test Results

   • Causes of hypoalbuminaemia
     • Protein deficiency (less protein intake results in the rapid loss of cellular ribonucleic acid and disaggregation of the endoplasmic reticulum–bound polysomes and less synthesis)
     • Defective synthesis (occurs in liver cirrhosis)
     • Extravascular loss (nehprotic syndrome cause great levels of proteinuria as the albumin is filtered out rather than being recycled)
     • Protein losing enteropathy (intestinal losses)
     • Excessive burns (the skin is a major extravasular stirage site for albumin and tissue damage can cause the levels to drop)
     • Haemodilution (lowers serum concentration)
     • Chronic inflammation (increased vesssel permeability, decreased synthesis)
   • Hypocalcaemia
     • in CKD less pohosphate is excreted, causing more PTH secretion and suppressing the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol
       • Less activated vitamin D causes less Ca2+ absorption from diet, so in compensation, more PTH released
         • PTH causes more Ca2+ breakdown from the bone. Bones become weak and brittle => renal osteodystrophy
           • The elevated PTH causes a high ̶ bone turnover lesion, known as osteitis fibrosa, develops. This is one of several bone lesions, which as a group are commonly known as renal osteodystrophy and which develop in patients with severe CKD
     • The kidneys help control the amount of phosphate in the blood. Extra phosphate is filtered by the kidneys and passes out of the body in the urine. A high level of phosphate in the blood is usually caused by a kidney problem. The amount of phosphate in the blood affects the level of calcium in the blood. Calcium and phosphate in the body react in opposite ways: as blood calcium levels rise, phosphate levels fall.

4. What are serum haptoglobins, direct Coombs test, haematinics?

   • Serum haptoglobins
     • This test measures the amount of haptoglobin(produced by liver) in the blood. Its purpose is to find and attach itself to free haemoglobin in the blood. This forms a complex that is rapidly removed from the circulation by the liver and the iron is then recycled
     • When large numbers of RBCs are destroyed, haptoglobin concentrations in the blood will temporarily decrease as the consumption of haptoglobin exceeds that produced by the liver.
   • Coombs' Test
     • A test for haemolytic anaemia. The sample is combined with Coombs' reagent and if there is agglutination then the test is positive
   • Haematinics
     • Test samples for serum Vitamin B12, Folate, Ferritin and Intrinsic Factor antibody assays

5. ECG interpretation and the effects of CKD on the Heart

   • ECG
     • Axis
       • The axis of the ECG is the major direction of the overall electrical activity of the heart. It can be normal, leftward (left axis deviation, or LAD), rightward (right axis deviation, or RAD) or indeterminate (northwest axis).
       • The QRS axis is the most important and to determine this, the limb leads (not the precordial leads) need to be examined.
         • The normal QRS axis should be between -30 and +90 degrees. Left axis deviation is defined as the major QRS vector, falling between -30 and -90 degrees.
           • If the QRS complex is upright (positive) in both lead I and lead aVF, then the axis is normal. If the QRS is upright in lead I (positive) and downward in lead aVF (negative), then the axis is between 0 and -90 degrees. However, recalling that left axis deviation is defined as between -30 and -90, this scenario is not always technically left axis deviation. In this scenario, the QRS axis could fall between 0 and -30, which is within normal limits. To further distinguish normal from left axis deviation in this setting, look at lead II. If lead II is downward (negative), then the axis is more towards -120, and left axis deviation is present. If the QRS complex in lead II is upright (positive), then the axis is more towards +60 degrees, and the QRS axis is normal.
     • Left Ventricular Hypertrophy Criteria
       • Cornell criteria: Add the R wave in aVL and the S wave in V3. If the sum is greater than 28 millimeters in males or greater than 20 mm in females, LVH is present.
       • Modified Cornell Criteria: Examine the R wave in aVL. If the R wave is greater than 12 mm in amplitude, LVH is present.
       • Sokolow-Lyon Criteria: Add the S wave in V1 plus the R wave in V5 or V6. If the sum is greater than 35 mm, LVH is present.
       • Romhilt-Estes LVH Point Score System: If the score equals 4, LVH is present with 30% to 54% sensitivity. If the score is greater than 5, LVH is present with 83% to 97% specificity
         • . Amplitude of largest R or S in limb leads ≥ 20 mm = 3 points. Amplitude of S in V1 or V2 ≥ 30 mm = 3 points. Amplitude of R in V5 or V6 ≥ 30 mm = 3 points. ST and T wave changes opposite QRS without digoxin = 3 points. ST and T wave changes opposite QRS with digoxin = 1 point. Left Atrial Enlargement = 3 points. Left Axis Deviation = 2 points. QRS duration ≥ 90 ms = 1 point. Intrinsicoid deflection in V5 or V6 > 50 ms = 1 point
   • Heart Failure
     • Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is strongly associated with mortality in these patients
       • Heart failure (HF) is the leading CV complication in CKD patients and its prevalence increases with declining kidney function. Abnormalities of left ventricular (LV) structure and function are very common in CKD and ESRD patients.
     • From a hemodynamic view, LVH is an adaptive remodeling process of the LV, which compensates the increase in cardiac work induced by an increased afterload (pressure overload), an increased preload (volume overload), or both.
       • Increased afterload may result from arterial hypertension, arterial stiffness, or valvular aortic stenosis and typically leads to a concentric thickening of the LV wall (concentric hypertrophy), which is meant to boost the intraventricular systolic pressure. Increased preload may be due to hypervolemia, anemia, and (in HD patients) high blood flow arteriovenous fistula; volume overload leads to the development of LV dilatation (eccentric LVH), by accumulation of new myocardial sarcomeres in series.
     • A large number of nonhemodynamic factors also contribute to the development of LVH and cardiomyopathy in CKD patients. These include hyperphosphatemia, excess angiotensin II, high serum aldosterone and sympathetic overactivity

6. Investigations for CKD

   • Renal biopsy
     • Biopsy is not usually indicated when renal US reveals small, echogenic kidneys, because this finding represents severe scarring and chronic, irreversible injury.
   • GFR
     • A GFR test is used to help diagnose kidney disease at an early stage, when it is most treatable. GFR may also be used to monitor people with chronic kidney disease (CKD) or other conditions that cause kidney damage. These include diabetes and high blood pressure.
       • GFR = Uinulin x V/Pinulin = Cinulin, where GFR = glomerular filtration rate in mL/min or mL/24 hr; Uinulin = urine concentration of inulin in mg/mL; V = urine flow rate in mL/min or mL/24 hr; Pinulin = plasma concentration of inulin in mg/mL; Cinulin = clearance of inulin in mL/min or mL/24 hr.
     • Using GFR to characterize chronic kidney disease (CKD) requires an understanding of its physiological variation, as well as its decline with healthy aging. The measurement of GFR is based on the urinary or plasma clearance of an ideal or near ideal exogenous marker such as inulin
     • An estimated (eGFR) is more commonly used
     • After age 2, GFR regulation is established, and when adjusted for body surface area, GFR is constant. In middle age, there is a gradual reduction in renal blood flow and GFR. The decline in kidney function is progressive but highly variable. There is a vast reserve in normal renal function, so the age-related decline does not usually present a problem.
     • Normal GFR is about 120 mL/min in men and 100 mL/min in women.
     • Blood flow to the glomerulus is regulated by the afferent and efferent arteriolar sphincter tone, which adjusts glomerular filtration pressure. Afferent arteriolar dilation or efferent arteriolar constriction increase the filtration fraction and GFR. This autoregulatory mechanism is capable of maintaining GFR across a wide range of blood pressures
       • If blood pressure falls, there is a decrease in RBF and reduction in afferent arteriolar pressure as well as a decrease in filtered solute. This triggers release of renin by the macula densa in the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I, which is subsequently converted to angiotensin II ACE in the lungs. Angiotensin II causes thirst (and water intake), vasoconstriction, and Na+ and water retention (via aldosterone), all of which increase blood pressure, renal perfusion pressure, and RBF. Additionally, the kidney responds to low levels of catecholamines circulating when blood pressure drops by preferential efferent arteriolar vasoconstriction, which maintains GFR.

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