Renal System Week 2

glomerular disease

Image result for glomerular disease A number of different diseases can result in glomerular disease. It may be the direct result of an infection or a drug toxic to the kidneys, or it may result from a disease that affects the entire body, like diabetes or lupus. Many different kinds of diseases can cause swelling or scarring of the nephron or glomerulus.

Continous buffering is through:

Mainly the Carbonic Acid Buffer system combined with excretion of CO2 by respiration (Fast acting) and secretion of H+ by the renal tubules for elimination of urine (slower acting) **This ensures equilibrium between H+ production and exrection**

Post-renal AKI

Obstruction or infection of the urinary tract (between the end of the kidney nephrons and the termination of the urethra) (Obstruction of urine outflow from the kidney)

Renal synthesis of vitamin d

The renal synthesis of calcitriol is tightly regulated by two counter-acting hormones, with up-regulation via parathyroid hormone (PTH) and down-regulation via fibroblast-like growth factor-23

Acids and Bases in the Body: H+ output

Ventilation: CO2 (+ H20) Renal: H+

Compensation:

When a primary respiratory or metabolic pH disturbance occurs, the other system (lungs or kidneys) will attempt to change pH in the opposite direction to compensate. Eg. in an individual with metabolic alkalosis which drives pH up, the respiratory system will attempt to compensate by driving pH back down. It is achieved through retaining C02 or hypo-ventilating (Slower breathing).

Acute Tubular Necrosis

is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI. Common causes of ATN include low blood pressure and use of nephrotoxic drugs. - destruction of nephron tubule cells- v. sensitive to ischaemia and toxins. - most frequent in people with major surgery, severe hypovolemia, sepsis, trauma or burns. - Many drugs are nephrotoxic- kidney concentrate to high level- thus more vulnerable. - Frequently reversible- requires recovery of injured cells, rmeoval of necrotic cells and regeneration of cewlls to restore tubule.

Chronic Pyelonephritis

is continuing pyogenic infection of the kidney that occurs almost exclusively in patients with major anatomic abnormalities. Symptoms may be absent or may include fever, malaise, and flank pain. Diagnosis is with urinalysis, culture, and imaging tests.

Arterial Blood Gases (normal range)

pH: 7.35-7.45. PaCO2: 35mmHG-45mmHg PaO2: 80mmHg-100mmHg HCO3-: 22mmol/L-26mmol/L Sa02: 95-100%

Additional important roles of the kidneys- they are involved in:

- Ca 2+ regulation through the production of active Vitamin D - RBC (erythrocyte) production through the secretion through the secretion of Erythropoietin.

AKI Risk:

- Common threat to seriously ill (mortality rate 25-80% depending on cause and clinical satus) - High rate of poor outcomes related to common presentation in elderly people with other acute (traumatic, shock, sepsis) and chronic (hypertension, diabetes) conditions. - After 30 yrs, GFR decreases by 10ml/min every decase- less reserve when elderly.

Where can a pH disturbance originate:

- Digestive system- vomitting and diarrhoea. - Renal System- reduced H+ secretion with CKD. - Musculoskeletal system: increased lactic acid production. - Metabolic system: ketoacid prodcution from fat breakdown. - Ingestion- consuming acidic or alkaline foods/drugs. - Respiratory: disturbances are caused by hyper or hypo-respiration.

Intra-renal causes of AKI

- Disorders of glomerular function (glomerulonephritis) - Tubular and interstitital disorders (pyelonephritis & acute tubular necrosis)

Erythropoietin (EPO)

"PRODUCING ERYTHROCYTES/RBCs" - Decreased levels can lead to anaemia. - Increased levels can lead to polycythaemia. Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. The kidney cells that make erythropoietin are sensitive to low oxygen levels in the blood that travels through the kidney.

Gentamicin Nephrotoxicity causes:

- Gentamicin is excreted by proximal convoluted tubules of the nephron, taken into the tubules cells- having a half life 100X of that in other tissue- it accumlates insde the cell. It reacts with other molecules- break down phospholipids- the major molecule forming cellular membrane. CAUSES ACUTE TUBULAR NECROSIS- breakdowqn of renal tubular system. With normal kidney function at normal dose- no toxicity. With renal insufficiency all gentamicin in the system must be eliminated by the remaining nephrons: - Accumulation occurs, acute tubular necrosis may occur. - AKI may result - Can have structural change and scarring - GFR reduction - Can cause further progression of CKD.

Two main organs involved in buffering:

- Lungs (Regulation of CO2 levels) - Kidneys (Regulation of H+ ions)

Acute Kidney Injury Classification (3)

1) Pre-renal 2) Intra-renal 3) Post-renal

H+ can be converted into

CO2

Most important buffer in the body

Carbonic acid buffer system.

H20 increased by ADH:

Decreased by absense of ADH.

Measured on pH scale is the:

Power of hydrogen.

90% of AKI happen in

Pre-renal and Intra-renal stages.

Endocrine secretion: erythropoietin (EPO):

EPO regulates red cell mass in response to tissue hypoxia. It is a cytokine (protein signaling molecule) for erythrocyte (red blood cell) precursors in the bone marrow. Human EPO has a molecular weight of 34 kDa. Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and proximal convoluted tubule.

Acids and Bases of Pure water.

In pure water, the base is OH- because it can bind to H+to form H20. Pure water has a neutral pH meaning that it is neither acidic or basic, the number of H+ and OH- are equal. pH (7)

CKD and COPD and EOP

Kidney disease is caused by a disruption in EPO production.

The organ that can remove H+ alone, without using any buffer:

The kidneys

Vitamin D3

cALCITRIOL

H+ Secretion is at 3 locations along the nephron

- Proximal Tubule - Thick ascending loop of henle. - Late distal tubule and collecting duct.

Why cant we use respiration (only) to regulate pH?

- To make CO2 (H+ must combine with HCO3-_ - The base buffer is used up when H+ is removed by this method,. -

pH disturbances can be (2) types:

1) Respiratory: disturbances are caused by hyper or hypo-respiration. 2) Metabolic: disturbances include anything that is non-respiratory (digestive,renal, musculo, etc)

If pH falls below 7.35

Acidosis- caused by too much acid or too little base.

K+ & H+ and renal system

Reduced by aldosterone.

Acidosis:

Respiratory acidosis: results from any condition that impairs/reduces respiration (Eg chronic and obstructive lung conditions, asphyxia). Metabolic acidosis: results from either too much acid of metabolic origin (ketoacidosis in DM, consuming acidic drugs) or too little base (Severe diarrhoea- excretes bicarbonate before it can be reabsorbed).

Na+ and Cl & renal disease

Is increase by aldosterone, decreased by atrial natruetric peptide.

Why is blood pH maintained within a narrow range

- 7.35-7.45- slightly more alkaline than pure water. - Low H+ concentration maintained because: - Hydrogen ions are very small and mobile (Reactive). - Charged and very reactive. - Tend to displace other cation in molvules. - change molecular structures. - therefore change molecular function. - proteins are particulary susceptible. - Transport molecules, enzymes, contractile molecules. When they contact protein they change shape

Renal Disorders:

- Acute or chronic deterioration in kidney function. - Acute kidney injury (AKI)- develops rapidly (hours to days) may not involve loss of nephrons, often fully resolves but can be life threatening. - Chronic kidney disease (CKD)- slower (months to years) involves progressive loss of nephrons and filtering capacity over time. - CKD- caused by damage due to other chronic diseases such as hypertension and DM, but also diseases of the kidney tissue (polycystic kidney) - Severe and unresovled AKI may lead to a progressive loss of nephrons and CKD.

AKI Diagnosis- Clinical assessment:

- Blood urea/creantine, pH, K+, Ca2+ (and other electrolytes), albumin. - Volume status (overload or depletion) - Urinalysis. - Imaging- ultrasound, X-Ray, biopsy.

Treatment of AKI

- Idenfication of the cause (pre,intra,post?) - Elimination of the triggering insult (nephrotoxin or infection) and/or instituion of disease-specific therapies. - Prevention and management of uramiec complications. - Dialysis - Nutritional management- sufficient protein and energy to regenerate kidney and maintain skin integrity, wound healing and avoid infection. Can take weeks/months to heal completely- may require dietary changes and medication.

Buffers Systems inside the cells:

- Inside RBC- haemoglobin can bind H+ (tends to displace O2 releasing it tyo the tissues- important buffer system during intense exercise, when there is increased acid production). - The phosphate buffer system- components are: H2PO4- (acid) & HPO4 2- (base) - BUT the ECF carbonic acid is the most important clinically.

Symptoms of AKI- patient experience:

- Often no initial symptoms Symptoms include: - Urinating less (oliguria) or not urinating at all (anuria). - Blood in urine or red/brown urine. - Sweelling (especially legs or feet) - Vomitting (or appetite loss) - Weakness/tiredness - Confusion or altered personalility - Seizures- waves of abnormal electrical acitivity in the brain, can cause fainting).

Treatment of Acid-Base disturbance

- Original cause investigated and treated- pH imbalance is a sign- not a disease itself. - Support compensatory mechanisms (eg lungs or kidneys) - HCO3- administration (NaHCO3 or CaHCO3). - Noninvasive ventilation (NiPPV or CPAP, BiPAP) - Invasive ventilation- intubation, mechanical ventilation (if sedated). - BP and circulatory control- fluid replacement if necessary, manage any other electrolyte imbalances.

Acute Kidney Injury (AKI)

- also known as Acute Renal Failure (ARF): - An abrupt and often reversible decline in the GFR. Characterised by: - Oliguria or anuria - Retention of water, H+, minerals, increased blood urea nitrogen (BUN), creatine and other waste products. - Reversible- dependent on abiliuty to remove/reverse causative agent (can lead to CKD). Causes: shock, renal toxicity, urinary tract obstruction.

Clinical Classification of Acid-Base Disturbances (4):

1) Metabolic acidosis 2) Metabolic Alkalosis 3) Respiratory Acidosis 4) Respiratory Alkalosis They are a sign, not a disease- THEY ARE CAUSED BY SOMETHING.

What can we tell from ABGs (6)

1) pH tells us if there is an acid-base disturbance (acidosis, alkalosis or neutral) 2) CO2 levels asre an indication of respiratory contribution (if CO2 is increased it is acidotic, if decreased it is alkalotic) 3) HCO3 levels are an indication of metabolic contribution (if HCO3 is increased its alkalotic, if ecreased it is acidotic) 4) Which label (CO2 or HCO3-) matches pH label (tell the origin of diturbance- respiratory or metabolic) 5) Are either the CO2 or HCO3- labels opposite to the pH (if so, the system is compensating for the disturbance) 6) If PaO2 and Sa02 are low- hypoxaemia is present.

Urine pH

5-8- urine is our 'drain' for excess H+

Unideal parameters for blood pH

6.5 and less or 7.8 and above.

Dehydrocholestrol

7-Dehydrocholesterol is a zoosterol that functions in the serum as a cholesterol precursor, and is converted to vitamin D₃ in the skin, therefore functioning as provitamin-D₃.

Bloods pH

7.35-7.45- tightly controlled as it has restricted limits for cellular function.

Pre-renal AKI

Acute reduction in kidney perfusion (hypo-perfusion) due to: - hypotension - hypovolaemia - decreased cardiac output or reduction in renal blood supply due to infection, inflammation, structural changes, toxicity and drugs. ( Marked decrease in renal blood flow)

Nephroxocity

Agents that are toxic to the liver (gentamicin)

If pH rises above 7.45

Alkalosis- is caused by too much base or too little acid.

First line of defense for pH

Buffers. Buffers system prevents large changes in pH by binding or releasing free H+ Ions.

Acids and Bases in the body: H+ input

Fatty acids and amino acids (from diet) CO2 (& H20) lactic acid and ketoacids through metabolism.

CO2 can be converted into:

H+

Buffer components.

H2CO3 (acid) and HCO3- (base)

Acids and Bases in the Body: buffers

HCO3- in extracellular fluid, proteins, hemoglobin & phosphates in the cell. Phosphates and ammonias in urine. Which is moved through ventilation or through the renal system.

Ca2+ and renal system

Increased by the parathryiod hormone.

Clinical Definition of AKI

Kidney disease improving goal outcomes (KDIGO) defines AKI as any of the following: - Increase in serum creatinine level by 0.3mg/dL or more within 48 hours - Increase in serum creatinine to 1.5 times baseline or more within the last 7 days - Urine output less than 0.5mL/kg/hr for 6 hours./

pH (Definiton):

Measure of free hydrogen ions (H+) in solution.

Alkalosis:

Respiratory alkalosis: results from any condition that increases respiration (hyperventilation). Metabolic alkalosis: results from either too much base of metabolic origin (ingestion of bicarbonate or absorbable antacids) or too little acid (eg vomitting or gastric drainage).

Acidic Solutions:

When H+ is added to a solution it becomes more acidic (less basic).. pH less than 7. When a base is added to a solution it becomes less acidic (more basic) having a pH greater than 7.

Intra-renal AKI

Within the kidney tissue: - Trauma - Ischaemia - Obstruction - Inflammation - Toxicity To glomerulus, nephrons tubules or interstitium. (Damage to structures within the kidney)