Urine Formation

Created by Musango07/04/11

The kidney converts blood plasma to urine in three stages

1. Glomerular filtration
2. Tubular reabsorption and secretion
3. Water conservation 

 Glomerular Filtration

•As fluid travels through the nephron, its composition changes, thus its name

–Glomerular filtrate- fluid in the capsular space that is similar to blood plasma except that it has almost no protein

–Tubular fluid- fluid from the PCT through the DCT

•Differs from the glomerular filtrate in that substances are removed and added by the tubule cells

–Urine- fluid that enters the collecting ducts

• Components of Filtration

Filtration membrane- the barrier through which the fluid must pass to enter the capsular space. Consist of:

-          The fenestrated endothelium of the capillary-  the honeycombed structure of the capillary endothelium, containing large pores that allow various substances to pass through (not blood cells or large proteins)

-          The basement membrane- Its structure is like a kitchen sponge. While blood plasma is 7% protein, the glomerular filtrate is only 0.03% protein.  It has traces of albumin and smaller polypeptides, including some hormones.

-          Filtration slits- octopi like structure of the podocytes. Each arm has numerous little extensions called pedicles (foot processes) that wrap around the capillaries and interdigitate with each other. Pedicles have a negatively charged filtration slits; this restricts anions like albumins from being filtered.

–Water, electrolytes, glucose, fatty acids, nitrogenous wastes, and vitamins are filtered.

–Some substances that are of low molecular weights are retained in the blood plasma because they are bound to plasma proteins e.g. Calcium, iron, thyroid hormone and plasma fatty acids. The small fraction of the above that are unbound will pass through

•About 20% of the plasma that passes through the kidney gets filtered into the nephron

•Filtration  takes place in the glomerulus

•It is driven by the hydrostatic pressure of the blood (osmosis (oncotic pressure) opposes filtration, but the hydrostatic pressure is larger)

•Water and small molecules are filtered; blood cells and large molecules (most proteins) do not pass through the filter 

•  Kidney trauma and infections can damage the filtration membrane and allow albumin or blood cells to filter through

1. Proteinuria (albuminuria)- the presence of protein in the urine

1. Hematuria- the presence of blood in the urine

•Strenuous exercise can temporarily cause proteinuria or hematuria

–Strenuous exercise greatly reduces perfusion of the kidney causing glomerular damage due to prolonged hypoxia.

1. Albuminuria

•More than the normal amount of albumin in the urine. Albumin is the predominant protein in human blood and it is the key to the regulation of the osmotic pressure of blood.

•It is normal to have some albumin in urine. But too much albumin indicates that protein is leaking through the kidney.

•Albuminuria can mean many things. For example, albuminuria may be a sign of significant kidney disease or it may simply be a sequel of vigorous exercise. Albuminuria is a form of proteinuria.

1. Hematuria

•is a sign that something is causing bleeding in the genitourinary tract

•There are two types of hematuria,

–Microscopic- the amount of blood in the urine is so small that it can be seen only under a microscope.

–Gross (or macroscopic) - the urine is pink, red, or dark brown and may contain small blood clots.

1. Joggers hematuria

results from repeated jarring of the bladder during jogging or long-distance running.

•Reddish urine that is not caused by blood in the urine is called pseudohematuria. It may be caused by some drugs and some types of food. Find out from BNF

• Filtration Pressure

•Glomerular filtration follows the same principles that govern filtration in other blood capillaries but with some  significant differences in the magnitude of forces involved

–The blood hydrostatic pressure is much higher, about 60mm Hg compared with 10-15 mm Hg in most other capillaries

–Results from the fact that the afferent arteriole is substantially larger (than those in other parts of the body) than the efferent arteriole, giving the glomerulus a large inlet and small outlet.

– The osmotic pressure (Oncotic) which opposes the hydrostatic pressure is comparatively lower.

1. Nephrosclerosis 

High blood pressure in the glomeruli makes the kidneys especially vulnerable to hypertension, which can rupture glomerular capillaries and lead to scarring of the kidney (Nephrosclerosis) and atherosclerosis of renal blood vessels, leading to renal failure

Glomerular Filtration Rate (GFR)

Is the amount of filtrate formed per minute by the two kidneys combined. GFR depends upon;

–Permeability of the filtration barrier

–Surface area of the filtration barrier

GFR measurement 

It a way of measuring kidney function. It is not measured directly. We use a marker substance, which is neither reabsorbed nor secreted by the kidney. The reasoning is: the amount of the substance excreted per minute should be equal to the amount filtered.

Two substances are used to measure GFR:

1. Inulin: a polysaccharide which is not metabolized by the body or reabsorbed from the urine. Inulin is not found in the body and must be injected. This substance gives the most accurate results and is used for research purposes.
2. Creatinine: a breakdown product from creatine phosphate, which is naturally found in the blood. Not quite as accurate as Inulin (about 10% is reabsorbed), but often used in medicine, since no injection is required.

Using Inulin in Measuring GFR

-          Is only filtered by the kidney; it is neither reabsorbed nor secreteted

-          Since no Inulin is reabsorbed from or secreted into the tubule, the amount filtered into the tubule at the glomerulus must equal the amount appearing in the urine

-          P X GFR = U X V ; where,

P = plasma concentration of Inulin, in mg/mL

GFR = glomerular filtration rate of plasma, in mL/min

U = urine concentration of Inulin, in mg/mL

V = rate of urine production, in mL/min

Solving the equation for GFR will give:

GFR = (U X V)/P

The normal value of GFR is 125ml/min

Renal Clearance

the volume of blood plasma from which a particular waste is completely removed in 1 minute.

Clearance= (U*V)/P

The clearance of Inulin= GFR and is taken as the standard, because it's neither secreted nor reabsorbed.

-          If a substance has a clearance greater than Inulin, then it must have been secreted into the tubular fluid by the nephron epithelium.

-          If it's lower, then either it was not filtered at the glomerulus or it must have been reabsorbed from the tubular fluid.

Regulation of Glomerular Filtration

GFR must be finely controlled:

If it is too high,

–Fluid flows through the renal tubules too rapidly for them to reabsorb the usual amount of water and solutes

–Urine output rises and creates a threat of dehydration and electrolyte depletion           

If it is too low

–Fluid flows sluggishly through the tubules and they reabsorb wastes that should be eliminated and azotemia may occur. GFR is adjusted by three homeostatic mechanisms:

1. Renal autoregulation- can even be observed in denervated kidneys e.g. transplanted kidneys!
2. Sympathetic control
3. Hormonal control

Renal Autoregulation

•The ability of the Nephrons to adjust their own blood flow and GFR without external (nervous or hormonal) control.

•Allows stable fluid and electrolyte balance in spite of alterations in mean arterial pressure.

•Therefore, a primary role of the renal autoregulatory mechanism is to regulate intrarenal haemodynamics and intrarenal pressures to levels that maintain an optimal balance with tubular metabolic functions.

•There are two mechanisms of autoregulation

• Myogenic mechanism

• Tubular glomerular feedback (TGF)

Myogenic Mechanism

Keeping mind that filtration pressure is a matter of blood pressure (or glomerular capillary pressure); Blood pressure changes are sensed through stretch receptors and respond accordingly through relaxation or constriction.

–afferent arteriolar vasoconstriction would serve to protect the glomerulus from uncontrolled systemic hypertension,

–while afferent arteriolar vasodilatation would allow for greater blood flow into the glomerulus in times of hypotension

The autoregulatory system accomplishes this by maintaining the glomerular capillary pressure around 60-70 mm Hg

Tubular glomerular Feedback

•The Juxtaglomerular apparatus (JGA) is made up of specialized cells in the wall of the afferent arteriole and granular cells in the wall of the distal tubule (the macula densa).

•This area is innervated by adrenergic fibers and the granular cells carry renin in intracellular granules

•The principle function of the JGA is adapting the GFR to early distal tubule fluid characteristics by modulating renin synthesis and release: this is known as the Tubular glomerular feedback (TGF) loop.  

•Afferent arteriolar caliber is principally controlled by TGF

•Besides altered sodium concentration at the macula densa of the distal tubule, release of renin can also be induced by changes in the blood flow patterns of the afferent arteriole, or by adrenergic stimulation.

Renin-Angiotensin Mechanism

•When blood pressure drops, the sympathetic nerves stimulate the JGA cells to secrete renin

•Renin acts on angiotensinogen to create angiotensin.

•Angiotensin is converted to angiotensin II by the action of angiotensin-converting enzyme (ACE) from the lungs and kidneys. Angiotensin II has multiple effects.

Renin-Angiotensin Mechanism

•Stimulates widespread vasoconstriction which raises the Mean Arterial Pressure throughout the body

•Constricts both the afferent and efferent arterioles (more prominent here because of greater concentration of Angiotensin II receptors) which reduces GFR and water loss

•Stimulates the secretion of antidiuretic hormone which promotes water reabsorption

•Stimulates the adrenal cortex to secrete Aldosterone, which in turn promotes sodium and water retention

•Stimulates the sense of thirst and encourages water intake

In summary, renal vascular resistance controlled by

•Intrinsic mechanisms

–Stretch receptors in wall of afferent and efferent arterioles

•Extrinsic mechanisms

–Hormones – renin-angiotensin II axis. Angiotensin II acts to increase efferent arteriolar tone

–Sympathetic innervation- in strenuous exercise or acute conditions such as circulatory shock. Norepinephrine directly increases afferent arteriolar tone causing a reduction in GFR and urine production, while redirecting blood from the kidneys to the heart, brain, and skeletal muscles.

Note: Angiotensin II release is dependent on renin release which results from

–blood flow changes in the afferent arteriole

–adrenergic stimulation

–solute changes at the macula densa 

Note: The normal GFR can only be maintained within systemic arterial pressures of 90-200 mmHg.

Circumstances under which GFR does not remain constant

1. Major heamorrhage- a large increase in sympathetic activity causes greater constriction of the afferent arterioles more than the efferent thus reducing GFR
2. Liver disease and malnutrition- reduces the plasma oncotic pressure considerably thus increasing GFR.

Assignment:

1. Define the terms; oliguria, polyuria, edema.
2. Describe the Pathophysiology of Glomerular nephritis.

Benzene Reactions

Summary of benzene reactions

Benzene is considered as the parent compound of aromatic hydrocarbons . Faraday in the year 1825 isolated from illuminating gas cylinders . In 1834 Mitscherlich  proposed the name benzene and the structure was proposed by Kekule . Aromatic hydrocarbons contain less number of hydrogens compared with aliphatic hydrocarbons . Benzene fits in the general formula C_nH_2n-6 .
Methods of preparation of benzene :
1. Benzene is prepared in the laboratory by distillation of sodium benzonate with soda lime .
                        C₆H₅COONa     +  NaOH        C₆H₆    +    Na₂CO₃
2. Reduction of phenol : Benzene can be obtained by the distillation of phenol with zinc dust .
                       C₆H₅OH   +  Zn      C₆H₆     +   ZnO
3. Polymerisation of actylene : When acetylene gas is passed through red hot iron or copper tubes it polymerises and gives benzene .
                      3 C₂H₂    C₆H₆

Reactions of Benzene

Benzene undergoes substitution reactions readily .
1. Halogenation : Benzene reacts with bromine or chlorine in the presence of Lewis acids like FeCl₃ , AlCl₃ , etc . to give corresponding halo-benzene .
            
Similarly with bromine , bromobenzene is formed .
2. Nitration : Benzene undergoes nitration when heated with a mixture of 1:1 ( by volume ) concentrated nitric acid and concentrated sulphuric acid ( nitration mixture ) at a temperature below 60^oC .
       
3. Sulphonation : Benzene reacts with fuming sulphuric acid and gives benzene sulphonic acid .
 
4. Friedel - Crafts alkylation and acylation : Benzene reacts with alkyl halides and acyl halides in the presence of Lewis acids ( AlCl₃ , FeCl₃ ) and gives alkyl benzenes and acyl benzenes .
 
Benzene reacts with acetyl chloride in the presence of anhydrous aluminium chloric and gives acetophenone  .

Addition Reactions

1. Halogenation : In the presence of finely divided nickel , under pressure , benzene undergoes hydrogenation to give cyclohexane .

2. Addition of halogens : Benzene undergoes addition reactions with chlorine or bromine in the presence of sunlight and gives hexachloro hexane or hexabromo cyclohexane .
 
3. Ozonolysis : One mole of benzene reacts with three moles of ozone and gives an ozonide which hydrolysis in presence of zinc and gives 3 moles of glyoxal .

Urinary System

Urinary System

Gross Anatomy

Consist of six organs

–Kidneys (2)

–Ureters (2)

–Urinary bladder

–Urethra

•Right slightly lower than left due to space occupied by liver

Renal parenchyma is divided into two zones

–Renal cortex- about 1cm thick

–Inner medulla

Micro Anatomy

•Each kidney contains 1.2 million functional units called Nephrons.

•A nephron consist of two principal parts

–Renal corpuscle- (glomerulus) where the blood plasma is filtered

–Renal tubule- processes the filtrate into urine

•Consist of a ball of capillaries called a glomerulus enclosed in a two-layered glomerular (Bowman's) capsule

Structure of the Bowman's capsule

In the glomerulus the filtrate of plasma has to pass through three layers:

-          The fenestrated epithelium of the capillary- the filtering membrane

-          The basement membrane of the bowman's capsule- It contains connective tissue and Mesangial cells which are both phagocytic and contractile.

-          The epithelial cells of the Bowman's capsule called podocytes which are wrapped around the capillaries.

• Renal Tubule
  

•Is a duct that leads away form the glomerular capsule and ends at the tip of a medullary pyramid

•Divided into four major regions

–Proximal convoluted tubule

–loop of Henle

–Distal convoluted tubule

–Collecting duct -(not really a part of the nephron- receives urine from many Nephrons

• Proximal Convoluted Tubule

–Longest and most coiled

–Simple cuboidal epithelium with microvilli (brush border for absorption capacity) and numerous mitochondria

• Loop of Henle

•Descending limb- first portion of the loop, passes from the cortex into the medulla

•At its deep end it turns 180^o and forms an ascending limb that returns to the cortex. 

•It is divided into thick and thin segments

–Thin segments- has a simple squamous epithelium

•Cells have low metabolic rate but are very permeable to water

•Forms the lower part of the descending limb, the bend, and partway up the ascending limb

–Thick segments- have a simple cuboidal epithelium with lots of mitochondria in the cells due to the high metabolic activity of active transport.

•Form initial parts of the descending limb and part or all of the ascending limb

• Distal Convoluted Tubule

•Shorter and less coiled than the PCT.

•Has a cuboidal epithelium with smooth-surface cells nearly devoid of microvilli

• Collecting Duct

•The DCTs of several Nephrons drain into a this straight tube, which passes into the medulla

•Are both lined with simple cuboidal epithelium

There are two populations of Nephrons:

•Cortical Nephrons- Nephrons close to the kidney surface

–Have shorter nephron loops that dip only slightly into the outer medulla before turning back

•Juxtamedullary nephron- Nephrons close to the medulla

–Have very long loops that extend to the apex of the renal pyramid

–Responsible for maintaining the salinity gradient

Blood Supply

•Receives 21% of the cardiac output

•Each kidney is supplied by a renal artery (sometimes 2 or more)

•The interlobular artery branches off afferent arterioles to the glomerulus of each nephron

•The glomerulus is drained by an efferent arteriole

Nerve Supply

•Renal nerves arise from the superior mesenteric ganglion and enter the kidney at the hilum.

•They follow the branches of the renal artery to innervate each nephron

•Consist mostly of sympathetic fibers that regulate blood flow into and out of each nephron thus controlling the filtration rate and urine formation

Functions of the kidney

-The main function is to regulate the volume and composition of the ECF.

-Excrete metabolic wastes e.g. Urea

-Excrete foreign substances and their derivatives .g. Drugs and food additives

-synthesize Prostaglandins and kinins which act within the kidney

-Function as an endocrine organ; produces EPO, renin, Calcitrol (The active form of Vit D)

Blood and Blood Clotting

BLOOD & clotting

Specific Objectives

1.       describe the mechanisms that contribute to blood clotting  

2.       identify the stages involved in blood clotting

3.       describe how chemicals called serotonin and Thromboxane A2 (released by platelets) play a role in Haemostasis

4.       describe the terms used to describe the difference between stationary versus moving blood clots

5.       describe the similarities and differences between the extrinsic and the intrinsic pathways of blood clotting

6.       describe the role of vitamin K in blood clotting

7.       list the 4 common blood types of the ABO blood group system

8.       describe which antibodies are found circulating in each of the respective ABO blood types (if any)

9.       Describe the Rh antigen.

10.   distinguish between the terms Rh negative and Ph positive  

11.   describe the complications that can occur when there is a mismatch between a mother who is Rh positive and a baby who is Rh negative , and what if anything that can be done to prevent problems.

Definition: The sequence (cascade) of reactions that prevent blood loss from a broken vessel.

 It's a fast, localized, and carefully controlled process. It occurs within seconds to minutes of the injury. Has three phases:

1. Vascular spasms – constriction of damaged blood vessels. Triggers include:

-          Direct injury to vascular smooth muscle

-          Presence of chemicals released by endothelial cells and platelets especially serotonin.

-          Reflexes initiated by local pain receptors

2. Platelet plug formation – sealing the vessel walls .Platelets adhere to exposed collagen fibers, become sticky, and form spiked processes. Attachment to collagen fibers activates the release of several chemicals including:

-          Serotonin – enhances the vascular response

-          Adenosine diphosphate (ADP) – attract platelets to site of injury

-          Thromboxane A2 – stimulates positive feedback cycle

-          PGI₂ limits the platelet plug formation to the site of injury

3. Coagulation or blood clotting – Blood clotting (coagulation) is normally complete within 3-6 minutes after blood vessel damage. In summary blood is transformed from a liquid to a gel. Consists of three crucial steps:

-          Formation of prothrombin activator. Step 1 can be divided into Two Separate mechanisms, called the Intrinsic Pathway and the Extrinsic Pathway. Intrinsic Pathway is initiated from damage from within the blood vessel (e.g., damage to endothelial lining exposes Collagen Fibers that, in turn, activate clotting factors within or intrinsic to the blood).  Platelets participate. Extrinsic Pathway-activated by chemicals released from damaged tissue, that is by factors Outside (Extrinsic to) the blood.

 Note:  Extrinsic Pathway has Fewer Steps than the intrinsic pathway, and, thus, is more rapid than the intrinsic pathway (e.g., in cases of Severe Tissue Trauma, the Extrinsic mechanism may clot blood within 15 seconds).
       :  a typical cut on the skin will activate both the Extrinsic and the intrinsic pathways.  How?  Well, damaged tissues in the area of the cut will activate the extrinsic pathway.  Also blood vessel damage inside the skin will exposes collagen fibers that activate clotting factors Intrinsic to the blood (the intrinsic pathway).
Disease Atherosclerosis might put one at risk for activation of the intrinsic pathway.  Narrowing of blood vessels----> increased Blood Pressure ----> increased risk of damaging blood vessels from within.  Thus, there is increased risk of blood clot formation of person with "hardening of arteries."
-The liver synthesizes many of the clotting factors present within the blood.  Almost all of these clotting factors exist in an inactive form until they are acted upon by something else.  Clotting Factor X is common to both intrinsic and extrinsic pathways.
 --exists in an inactive form until acted upon by intrinsic or extrinsic pathway.
Extrinsic pathway:  tissue factor TF, clotting factor VII activate---> Activated Factor X.
Intrinsic pathway:  platelet Factors XII, XI, IX, and VIII act on Factor X (inactive) ---> Activated Factor X.

-          Conversion of prothrombin to the active enzyme called thrombin

-          Activation of Fibrinogen to Fibrin by thrombin. Which forms a mesh that traps blood cells and seals the hole until the blood vessel can be permanently repaired.

Anticoagulants inhibit clot formation (e.g. Heparin, warfarin)

-unneeded clots are removed when healing has occurred (within 2 days of clot formation) by Fibrinolysis to prevent vessel blockage. Plasmin is the active digesting enzyme responsible for Fibrinolysis and is confined to the clot

Vitamin K is necessary for the synthesis of 4 clotting factors prothrombin (II), VII, IX, and X)

Calcium is also necessary for proper blood clotting.  Chelators like EDTA and Citrate Phosphate Dextrose will bind up the calcium in a test tube, and prevent the blood from clotting.  Useful in "blood banking" clinics.

Factors Limiting Clot Growth or Formation:

-          Size of clot is limited by the rapid removal of clotting factors and inhibition of activated clotting factors

-          Heparin is released in small amounts to inhibit thrombin activity

-          Unwanted clotting is prevented by the secretion of antithrombic substances (PGI₂ and heparin) secreted by endothelial cells; vitamin E is also a potent anticoagulant

Fibrinolysis – removal of unneeded clots when healing has occurred (within 2 days of clot formation)

• Prevents vessel blockage
• Plasmin is the active digesting enzyme responsible for Fibrinolysis
• Plasmin action is confined to the clot

Mechanism - plasminogen (a plasma protein) is activated by many factors & becomes Plasmin. Which then breaks down fibrin meshwork & phagocytic WBCs remove products of clot dissolution

        Factors Limiting Clot Growth or Formation

o   Size of clot is limited by the rapid removal of clotting factors and inhibition of activated clotting factors

o   Heparin is released in small amounts to inhibit thrombin activity

o   Unwanted clotting is prevented by the secretion of antithrombic substances (PGI₂ and heparin) secreted by endothelial cells; vitamin E is also a potent anticoagulant

Clinical Disorders of Haemostasis – Can be due to improper clot formation or the inhibition of natural clot formation

1.      Thromboembolytic Conditions – result from undesired clot formation:

• Thrombus – a stationary blood clot.  a clot that develops in an unbroken vessel. can block circulation and kill viable tissues
• Embolus – a mobile "moving" blood clot in the bloodstream. Dangerous if it encounters narrow vessels. if it lodges in lungs, called a Pulmonary Embolism.
• Embolism – clot obstructing a vessel
• Disseminated Intravascular Coagulation (DIC) – bacterial toxins cause clotting in healthy tissue; the remaining blood in the system is unable to clot and patient experiences heavy bleeding.

 Treatment: aspirin, heparin, and dicumarol are used to prevent unwanted clotting

2.      Bleeding Conditions – normal clot formation is inhibited

• Thrombocytopenia – due to a platelet deficiency

§  Seen in patients with bone marrow disorders; people exposed to ionizing radiation (ex. X-rays); and certain drugs

§  Spontaneous bleeding occurs in these individuals and Haemostasis cannot occur because of platelet deficiency

§  As a consequence of this, the patient may experience bruising and the formation of purplish spots on the skin.

• Liver Impairment – causes are reduction in the production of procoagulants needed for the clotting response.

• Vitamin K deficiency – due to lack of vitamin K in the diet (rare) or because antibiotic use has disrupted the intestinal flora responsible for making vitamin K. Prothrombin Synthesis in the liver requires the presence of Vitamin K.

-          Disruption in fat absorption, especially in the intestines – Vitamin K is fat-soluble and any disruption involving lipids or fat will impair vitamin K absorption

-          Disruption in bile production or a bile duct obstruction - The salts present in bile are critical for vitamin K absorption in the intestines; imbalances or disruptions will also impair vitamin K absorption

-          prolonged antibiotic therapy (decreases bacteria that make Vitamin K)

• Hemophilias - genetic 'defect' that leads to inability to produce certain clotting factor(s). Temporary treatment is by infusion with whole blood.
• Anticoagulant therapy (e.g., heparin--acts as an anti-thrombin; coumadin--interferes with liver's utilization of Vitamin K; that is, coumadin is a vitamin K antagonist).  Note:  another name for Coumadin is Warfarin or Dicumarol.

Transfusions and Blood Typing

·         The word "antigen" means Antibody Generating. A person will produce antibodies against blood group antigens that are foreign (not on the surface of one's own red blood cells). For some 80% of the population, the ABO blood group antigens are also present in salivary secretions (saliva).

·         Antigens (agglutinogens) present on the surface of red blood cells can cause adverse reactions in transfusion recipients. They are glycolipids or glycoproteins.

·         Prior to receiving transfusions a patient's blood type must be determined and the blood they receive must match to avoid complications

·         The following agglutinogens are screened in all cases: ABO and Rh

ABO Blood Typing

determined by the presence or absence of AB agglutinogens (Antigens) on RBC cell membranes. An individual with type AB:

• Both the A and B antigens are present on RBC cell membrane
• Antibodies against A and B antigens are not produced in the individual
• AB individuals can receive A, B, AB, or O blood transfusions (Universal Recipient)
• AB individuals can only donate to AB individuals

• An individual with type A:
• Only the A antigens are present on the RBC cell membrane
• Antibodies against B antigens are produced in the individual
• A individuals can receive A or O blood transfusions
• A individuals can only donate to A or AB individuals

• An individual with type B:
• Only the B antigens are present on the RBC cell membranes
• Antibodies against A antigens are produced in the individual
• B individuals can receive B or O blood transfusions
• B individuals can only donate to B or AB individuals

• An individual with type O:
• Neither A nor B antigens are present on the RBC cell membranes
• Antibodies against A and B antigens are produced in the individual
• O individuals can only receive O blood transfusions
• O individuals can donate to A, B, AB, and O individuals (Universal Donor)

Rh factor Blood Typing

determined by the presence or absence of at least 8 different types if Rh agglutinogens.

• An Rh⁺ individual:
• Rh agglutinogens are present on the RBC cell membrane
• No antibodies are formed against the Rh antigens in the individual
• Individuals can receive blood from Rh⁺ and Rh^- individuals, provided they have the correct ABO blood group

• An Rh^- individual:
• Rh agglutinogens are absent on the RBC cell membrane
• No antibodies are formed against Rh antigens unless the individual has prior exposure to them (ex. Transfusion Rh⁺ blood or delivery of an Rh⁺ baby to an Rh^-mother)
• Rh^- individuals can only receive Rh^- blood transfusions
• Rh^- can donate to Rh^- and Rh⁺ individuals (because of the absence of the Rh antigen on the RBC cell membrane), provided they have the correct ABO blood group

Pregnancy and Rh^- Individuals

• If the fetus of an Rh^- mother is Rh⁺, the mother will produce large amounts of antibodies to the Rh antigen when the placenta detaches and the fetal blood is mixed with the maternal blood.  This first pregnancy will not be affected. 

Following delivery (live or dead), the mother must receive a shot containing antibodies against the Rh antigen. This will inhibit an immune response against an Rh⁺ fetus in future pregnancies.  This will prevent severe birth defects in the fetus and improve chances of a successful pregnancy; Hemolytic Disease of the Newborn (HDN).

Plasma and Blood Volume Expanders

• Clinical use:  colloidal or isotonic salt solutions are used in emergency situations in which the patient is experiencing severe blood loss and immediate blood transfusions are not available.  Plasma and blood volume expanders will only bring the blood volume back to normal, not increase the levels of the formed elements.
• Colloid solutions – e.g. Dextran and purified human serum albumin – used to replenish plasma volume
• Isotonic salt solutions – e.g. Normal saline, Ringer's solution – used to increase blood volume by increasing water volume

1. Define and classify the various forms of Anemia
2. Explain the roles of Vitamin K, B12, EPO

Created by Musango 28/03/11

Essential Terminologies and Concepts of CVS

Essential Terminology and Concepts of CVS

Systole- each period of contraction

Diastole – each period of relaxation

Heart rate/Pulse rate (HR) - the number of times the heart contracts/beats per minute (Av.-75 at rest)

Stroke volume (SV) - the amount of volume ejected by each ventricle (equal for both ventricles- 70ml at rest)

Cardiac output (CO) - total volume each ventricle ejects per minute (= HR*SV) i.e. at rest CO= 70/min * 70ml= 4900ml/min or approximately 5l/min

Venous returns- amount of blood that returns from the veins to the heart per minute. Under normal circumstances = CO.

Hydrostatic pressure – the pressure exerted by the blood onto the walls of blood vessels. We have systolic and diastolic pressure.

Vascular resistance- the resistance of the blood vessels to blood flow.

–        Total Peripheral resistance (TPR) –The resistance of all blood vessels down stream to the Aorta.

–        Pulmonary vascular resistance (PVR) - The resistance of all blood vessels down stream to the Pulmonary artery.

        TPR is 7 times more than PVR. This is because the pulmonary blood vessels are shorter and wider than the systemic, and this is why the walls of the left ventricle are thicker and more muscular than the right. to over come the resistance.

Blood pressure- in the arteries average- 90-120mmHg, in the veins 1-2mmHg.

Þ    describe CCF, Aneurysm

Anatomical distribution of the CO- The distribution depends on the resistance of the arterioles in the region. Tissues with low vascular resistance receive a higher proportion of the CO. The resistance depends mainly on the diameter of the vessels. In certain circumstances these can be changed e.g. during exercise, the arterioles in the skeletal muscle dilate while those to the GIT constrict, thus allowing more blood to go to the skeletal muscle at the expense of the supply the GIT.

Þ    List the distribution of the CO in the body systems and the blood volume in the vascular system. (The veins keep 60% of the blood)

Þ    Why are the veins referred to as blood reservoirs? Why do women have less blood than males?

Þ    Define the term Haematocrit and state its significance to the blood flow.

Þ    Discuss the Mechanical events of the cardiac cycle and relate them with the electrical events in the following format:

1. Ventricular filling
2. Isovolumic ventricular contraction
3. Ejection
4. Isovolumic ventricular relaxation

Þ    Explain the origin of the heart sounds viz lubb, dup and murmurs

Þ    Differentiate the parasympathetic innervation of the heart from the sympathetic, in terms of their location and effects.

Þ    Define inotropic and chronotropic properties, tachycardia and bradycardia.

Þ    Explain why the heart rate will increase to about 100 beats/min, if you block both the sympathetic and parasympathetic flow to the heart.

Þ    Describe the structure of the various blood and lymph vessels.

The Blood

It is a tissue composed of:

-          a solid phase of formed elements- Cells and part of cells and

-          Liquid phase-plasma.

Lymph is formed from blood by filtration at the capillaries due to hydrostatic pressure. It's low in protein content as compared to the blood. It is returned to the venous circulation via the lymphatic vessels at the thoracic duct. The lymphatic vessels have one way valves. Along the way the fluid passes through Lymph nodes where it is inspected for foreign substances e.g. bacteria and they are filtered.

Blood constituents

1. RBC- carries and protects Haemoglobin.

Describe the structure of RBCs

Define the terms; red cell count, mean corpuscular volume, erythrocyte sedimentation rate and their significance.

2. WBCs (Leucocytes)

List the various types and their functions

3. Megakaryocytes and Platelets

-Platelets have no nucleus

-contain Golgi apparatus, ER, Enzymes, Microtubules and filaments.

-Functions- Haemostasis, Phagocytosis, storage and transport of 5-HT and Histamine.

4. List the constituents and functions of Plasma.

Functions of Blood

1.       Ionic and Osmotic balance- the blood proteins i.e. Albumins and Globulins are the ones that maintain osmotic pressure in the capillaries. (They do not cross the capillary walls due their size) this is called Oncotic pressure.

2.       Nutrition and excretion- transports nutrients, hormones, waste products, drugs and their metabolites.

3.       Blood gases

4.       Buffering

5.       Protection

6.       temperature control

7.       Turgor- controls tone of the skin, turgidity of the organs and provides the hydraulic pressure for the erection of the penis.

Created by: Musango 26/3/11