Normal Chemical Composition of Urine

Urine is an aqueous solution of greater than 95% water, with a minimum of these remaining constituents, in order of decreasing concentration:

Urea 9.3 g/L.

Chloride 1.87 g/L.

Sodium 1.17 g/L.

Potassium 0.750 g/L.

Creatinine 0.670 g/L .

Other dissolved ions, inorganic and organic compounds (proteins, hormones, metabolites).

Urine is sterile until it reaches the urethra, where epithelial cells lining the urethra are colonized by facultatively anaerobic gram-negative rods and cocci. Urea is essentially a processed form of ammonia that is non-toxic to mammals, unlike ammonia, which can be highly toxic. It is processed from ammonia and carbon dioxide in the liver.

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

• Intracellular (inside cells) = ~ 34 liters
• Interstitial (outside cells) = ~ 13 liters
• Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

• Capillary walls (1 cell thick) separate blood from interstitial fluid
• Cell membranes separate intracellular and interstitial fluids

• Loss of about 30% of body water is fatal

Ions = atoms or molecules with unequal numbers of electrons and protons:

• found in both intra- & extracellular fluid
• examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

• Giving up electron leaves a + charge (cation)
• Taking on electron produces a - charge (anion)
• Ions conduct electricity
• Without ions there can be no nerves or excitability
  • Na⁺ and K⁺ cations  
  • Ca²⁺ and Mg²⁺ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

• High K+ in cells, high Na+ outside
• Ion gradients maintained by Na pump (1/3 of basal metabolism)
• Think of Na+ gradient as a Na+ battery- stored electrical energy
• K+ gradient forms a K+ battery
• Energy stored in Na+ and K+ batteries can be tapped when ions flow

• Na+ and K+ produce action potential of excitable cells

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.

When blood vessels are damaged, fibrils of collagen are exposed.

• von Willebrand factor links the collagen to platelets forming a plug of platelets there.
• The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
• (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)

ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation. 

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting  contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.

The Body Regulates pH in Several Ways

• Buffers are weak acid mixtures (such as bicarbonate/CO₂) which minimize pH change
  • Buffer is always a mixture of 2 compounds
    • One compound takes up H ions if there are too many (H acceptor)
    • The second compound releases H ions if there are not enough (H donor)
  • The strength of a buffer is given by the buffer capacity
    • Buffer capacity is proportional to the buffer concentration and to a parameter known as the pK
  • Mouth bacteria produce acids which attack teeth, producing caries (cavities). People with low buffer capacities in their saliva have more caries than those with high buffer capacities.
• CO₂ gas (a potential acid) is eliminated by the lungs
• Other acids and bases are eliminated by the kidneys