raas system(renin angoitensin aldosterone )

RAAS systems is very important in our body because this control it is a part of homeostasis(control normality functioning of internal system).

RAAS can be divided into 2 parts:

1. plasmatic endocrine cascade 
2. local tissue RAAS- affecting heart , vessels, adrenal gland and brain) 

for plasmatic endocrine cascade , we can divided into 2 substances which are renin and angiotensin 1 (AT-1). renin synthesised as preprorenin in juxtaglomerular cells in kidney, then it will cleaved to prorenin which stiil inactive form and then finally to active renin. Renin is used to catalyze conversion of angiotensinogen produced by the liver into AT-1. Renin secretion will be secreted under certain condition which are:

1. when blood pressure drop in vas afferens
2. drop in sodium ion concentration detected by macula densa in distal tubule.
3. when increased in sympathetic activity(when noradrenaline and adrenaline bind to B1 receptor)

AT1 only have small to none its own physiological effect because AT-1 will be converted to AT-2 by angiotensin converting enzyme (ACE). ACE also responsible for bradykinin breakdown( bradykinin has vasodilator effect), ACE maily bound to endothelial membrane especially in pulmonary circulation.AT -2 has very shot half life , maximum inly 1 minute, because hydrolyzed by plasmatic peptidases. AT -2 has certain effect:

• cause vasoconstriction- increase peripheral vascular resistance.
• increase aldosterone secretion- cause sodium ion retention which lead to water retention
• tissue remodelling in vascular smooth muscle , fibroblast activation, collagen synthesis and cardiomyocyte hypertrophy and apoptosis.
• effect central nervous system by activate thirst center activation, increased sympathetic tonus and ADH and ACTH secretion.

hence if activation of RAAS system occur in chronic condition it can lead to many problem for example:

1. atherosclerosis
2. vascular hypertrophy
3. left ventricle hypertrophy fibrosis
4. decrease glomerular filtration rate 
5. protienuria 
6. sodium retention

this will lead to hypertension, that can lead to stroke, heart failure and renal failure finally lead to death.

how to loss weight?

everyone will desired to have slim body to look beautiful or good, not only for that, the most important is to take care of our health.

why obese is so dangerous?

ok, here i will explain a bit why being obese is danger for us.Obese willlead you to have a lot of disease for example diabetes mellitus, hypertension,atherosclerosis, hormonal dysbalance , problem to have childs, liver problem and most important is heart probblem. for more explaination you can comment later and i will explain it

so , how can we loss our weight:

1. first thing you need to keep in mind is, do not to try to loss weight more than 10kg in 6 months, because if you loss your weight to fast , it can lead to other problems.
2. you need to take balance diet: refer here: http://healthncarelifestyle.blogspot.cz/2014/03/get-balanced-diet.html
3. and also you need to make sure to reduce amount of food especially carbohydrate because carbohydrate if excess, it will change to fat in our bodies.
4. drink a lot of water, because it can prevent us to feel hungry and also we need enough water for metabolism in our bodies.
5. do exercise, 30 minutes everyday.
6. stop smoking 
7. the most important thing is to be motivated to do what you have planned.

case study 1

A 63 years old man with a long history of alcohol use presents to his new primary care physician with a 6 months history of increasing abdominal girth. He has also noted easy bruisability and worsening fatique. He denies any history of GI bleeding. He continues to drink three to four coktails a night but says he is trying to cut down. Physical examination reveals a cachectic man who appears older than his stated age. Blood pressure is 108/70 mm Hg. His scleras are anicteric . his neck vein are flat, and chest examination demonstrates gynecomastia and multiple spider angiomas. Abdominal examination is significant for protuberant abdomen with a detectable fluid wave, shifting dullness, and an enlarged spleen. The liver edge is difficult to appreciate. He has trace pitting pedal edema. Laboratory evaluation shows anemia, mild thrombocytopenia, and elevated prothrombin time. Abdominal ultrasounogram confirms a shrunken , heterogenous liver consistent with cirrhosis, significant ascites and spenomegaly.

Question:

1)       Describe possible mechanisms for alcohol induced cirrhosis.

2)       What is the proposed mechanism of portal hypertension, and how does it affect ascites formation?

3)       Significant hematologic abnormalities exist. How might they be explained?

Answer:

1)       The exact mechanism of alcohol induced injury to the liver is unknown; however , it is thought that the marked distortion of hepatic architecture , fibrous tissue deposition and scarring , and regenerative nodule formation result from multiple processes. Chronic alcohol use has been associated with impaired protein synthesis, lipid peroxidation , and the formation of acetaldehyde, which may interfere with membrane lipid integritiy and disrupt cellular functios. Local hypoxia, as well as cell mediated and antibody- mediated cytotoxicity, have also been implicated.

2)       Portal hypertension is in part responsible for many of the complication of cirrhosis, including clinically apparent ascites , a sign of liver disease associated eith poor long term survival. Although no single hypothesis can explain its pathogenesis, portal hypertension and inappropriate renal retention of sodium are important elements of any theory. Portal hypertension changes the hepatocellular architecture, resulting in increased intrahepatic vascular resistance. This elevates the sinusoidal pressure transmitted to the portal vein and other vascular bed. Spenomegaly and portal to systemic shunting result. Vasodilator such as nitic oxide are shuntrd away from liver and not cleared from thr circulation , resulting in peripheral arteriolar vasodilation. Decreased renal artery perfusion from this vasodilation is perceived as an intravascular volume deficit by the kidney, activated raas system causing sodium and water resorption. By overwhelming oncotic pressure , increased hydrostatic pressure from fluid retention in the portal vein result in ascitrs formation. Exceeding lymphatic drainage capacity, ascites accumulates in the peritoneum.

3)       Splenomegaly and hyperslenism are a direct consequence of elevated portal venous pressure. Thrombocytopenia and haemolytic occur as a result of both sequestration and these formed elements by the spleen and depressive effect of alcohol on the bone marrow. The frequent bruising and the elevated prothrombin time in this patient highlight the coagulopathy seen ic cirrhosis and chronic liver disease. As a result of inadequate bile excretion, there is impaired absorption of the fat soluble vitamin K, a vitamin necessary for the activation of specific clotting factors. In addition, inadequate hepatic synthesis of other  clotting factors causes a coagulopathy.

Bleeding into gastrointestinal tract

Sometimes , we did not realise that we having problem with our gut, and actually our gut undergo bleeding problem. So here , I will share with you different types of bleeding in gut.

Types:

1.       Hematemesis: this is bleeding characterise by vomiting of blood. It can cause by esophageal varises( cause by portal hypertension), esophegeal ulcer, mallory weis syndrome gastric ulcer. Patients usually vomits up bright red, undigested blood. But in gastric bleeding, the vomited blood is digested by gastric juices and has appearance of “coffee ground”.

2.       Melena: appear in feces with tarry black , semisolid appearance, foul smell, usually originate from upper git(stomach, small intestine). But to appear as melena, blood must be at least 50 -100ml.

3.       Enterorrhagia: appear as fresh, bright red blood on the feces, originate from lower git. Usually appear in patients with haemorrhoids, ulcerative colitis.

4.       Occult bleeding: blood that cannot recognize by naked eye, but we can use benzidine test. Usually originate in the upper git, when chronically can lead to iron deficiency anemia.

ANGINA PECTORIS-CHEST PAIN

What is angina pectoris?

Angina pectoris is pain that occur in the chest because of heart muscle undergo lack supply of oxygen or we called it ischemia. This pain present with central chest tightness or heaviness and may radiate to upper extremities( more often to the left) , to the neck and jaw. This pain usually occur during exertion and relieved by rest.

This disease can cause by certain things, most common is atherosclerosis especially in obese people who taking diet rich in cholesterol and hypertension. This also can cause by anemia, tachyarythmias, polycythemia, myocardium hypertrophy.

Types of angina:

1.       Stable angina: which is induced by effort(physical activity) and relieved by rest and also relieved by nitrogylcerin(vasodilator). Relieved within 5 minutes

2.       Unstable angina: angina with increasing frequency and severity associated with myocardial infarction . this pain last longer, more tha 20 minutes and not relieved by nitroglycerin.

3.       Prinzmetal angina: caused by coronary arteries vasospasm.

How to diagnoses:

·         First by physical examination. Ask about the pain.

·         ECG test. May show ST depression. But if resting ECG normal, we should use exercise ECG, thalium scan, cardiac ct or coronary angiography

How to manage the problem:

1.       First of all, we need to change our lifestyle by stop smoking, do exercise, and weight loss. Controlour blood pressure, diabetes mellitus, cholesterol level.

2.       Give aspirin(vasodilator)

3.       B blocker-reduce heart work, hence reduce heart metabolism.

4.       Nitroglycerin(vasodilator)

5.       Long acting calcium antagonist- reduce heart contractility.

sympathetic system: adrenergic receptors in human body

receptor for sympathetic system we called adrenergic receptors which are divided into 2 families: a receptors and b receptors.

a receptors:

1. a1 receptors:

• vasoconstriction : increase peripheral resistance and blood pressure
• glycogenolysis, gluconeogenesis in liver
• increase tone of sphincters in git and bladder
• decrease tone oof motility of git
• contraction of pregnanat uterus
• mydriasis by contraction of dilator pupilla muscle.

    2. a2 receptors:

• presynaptical localization: result in decrease release of noradrenaline
• postsynaptical localization: decrease insulin release by b cell, decrease motility , tone and secretion in git
• aggregation of platelets
• vasoconstriction
• inhibit acetylcholine release

b receptors:

1. b1 receptors:

• positive effect on heart: increase heart rate, contractility, dromotropic effect(conductivity), bathmotropic(excitibility)
• kidney-juxtaglomerular : increase renin secretion

2. b2 receptors :

• vasodilation of blood vessels in skeletal muscles and coronary arteries.
• bronchodilation
• relaxation of visceral smooth muscle
• increase muscle and liver glycogenolysis
• increase insulin release by b cells
• increase glucagon release
• increase salivation-thick
• decrease tone of bladder detrussor muscle
• decrease tone of uterine smooth muscle
• skeletal muscle tremor

3. b3 receptors

• lipolysis

Tubular function in the kidneys

Proximal convulated tubule(PCT)

-          Approximately 120ml/min of glomerular filtrate are generated in glomerulus.

-          In the PCTmost  of the filtered load reabsorb again which are water by osmotic activity (80%) most of the Na and under normal condition almost all K+ by passive diffusion(driven by  the positive tubule electrical potential present along the S2 and S3 segments and by paracellular solvent drag and glucose actively co transpot with Na from the tubular fluid.  Also have Na-H antiporter.

-          Number of substances also secreted by into tubular fluid for example creatinine, histamine many drugs and toxic.

Loop of Henle

-          Normally about 30ml/min of isotonic filtrate is delivered to loop oh Henle where counter multiplier mechanism can achieves concentration of the urine.

-          Loop of Henle important to make sure osmotic gradient for facultative water reabsorption from collecting tubule to prevent water loss by kidney. Along the descending limb of the loop of Henle, K is secreted into the tubule lumen from the interstitium. Along the thick ascending limb, K is reabsorbed via Na-K-2 Cl cotransport. In the loop, there is net K reabsorption of 25% of the filtered K. Na reabsorption is controlled by sympathetic system and aldosterone.

Distal convulated tubule(DCT)

-          In the distal convulated tubules there are facultative N and Ca reabsorption and K and P excretion controlled by aldosterone and parathyroid hormone.

Collecting duct

-          It contain 2 types of cells: principal cell and intercalated cell.

-          The principal cell mediates the collecting duct's influence on sodium and potassium balance via sodium channels and potassium channels located on the cell's apical membrane. Aldosterone determines expression of sodium channels with increased aldosterone causing increased expression of luminal sodium channels. Aldosterone increases the number of Na⁺/K⁺-ATPase pumps  that allow increased sodium reabsorption and potassium secretion. Vasopressin determines the expression of aquaporin channels on the cell surface. Together, aldosterone and vasopressin let the principal cell control the quantity of water that is reabsorbed.

-          Intercalated cells come in α and β varieties and participate in acid-base homeostasis

Type of cell	Secretes	Reabsorbs
α-intercalated cells	acid (via an apical H+-ATPase and H+/K+ exchanger) in the form ofhydrogen ions	bicarbonate (via band 3, a basolat-eral Cl-/HCO3-exchanger)[5]
β-intercalated cells	bicarbonate (via pendrin a specialised api-cal Cl-/HCO3-)	acid (via a basal H+-ATPase)

For their contribution to acid-base homeostasis, the intercalated cells play important roles in the kid-ney's response to acidosis and alkalosis.

nephrotic syndrome

What is nephrotic syndrome?

Nephrotic syndrome caused by increase in glomerular permeability to plasma protein. This syndrome can arise from nephritc syndrome when severe proteinuria occur which is daily loss of protein through kidneys is more than 3.5g/day.

Usually loss of proteins more than production by liver causing hypoproteinemia. When there is hypoproteinemia, oncotic pressure in the blood reduced causing formation of edema , edema usually can be detected in infraorbital region and lower limbs. Because of the body has lower protein concentration, liver will try to produce more protein but, there is not enough protein in the body causing liver produce lipoprotein resulting in hyperlipidemia usually formation of LDL, and cholesterol more than 10mmol/L. hyperlipidemia can cause increase risk of atherosclerosis.

Besides that , when there is low protein in the body , the substrate to produce immunoglobulin will decrease causing decrease resistance to infections.

Other than that, hypoproteinemia causing loss of anti coagulation factors resulting in hypercoagulability.

cystic fibrosis

Cystic fibrosis also known as mucoviscidosis because this disease cause formation of viscous mucus in lungs, pancreas and also testes.

This disease is hereditary autosomal recessive disease. cystic fibrosis can cause restriction to breathing because the mucus obstruct the lung and also fill the airspace with mucus that is very hard to remove by coughing.

Cystic fibrosis occur when genetic that codes for CFTR(cystic fibrosis transmembrane regulator) is defect causing formation of abnormal CFTR. Abnormal CFTR cannot regulate the chloride ions out the cells causing chloride ions trap inside the cells. this causing disbalance of electric charge inside and outside the cells causing movement of cation mainly sodium ions into the cells and result in formation of salt. when sodium channel is move into the cells , it cause osmotic pressure changes resulting diffusion of water into the cells resulting in dehydration and thick mucus.

when there is thick mucus in lungs, lungs cannot be cleaned properly causing recurrent infections result in chronic pneumonia and formation of lung fibrosis and finally result in cor pulmonale whic is right heart failure.

what is chronic bronchitis?

Chronic bronchitis:

defined clinically as cough and sputum production on ost days for 3 months of 2 successive years.symptoms improve if they stop smoking.

How chronic bronchitis develops:

When there is smoking or air pollution, this cause reduce ciliary and pahgocytary activity of epithelium resulting in mucus accumulation.

This lead to bronchi wall inflammation. Inflammatory infiltration of wall lead to edema resulting in obstruction of the airways. Ifnflammation produce exudate result in cough and expectoration. In small bronchioles , this lead to wall destruction eventually bronchiectasis.

When there is obstruction , its result in in prolonged expiration eventually air trapping causing hypoventilation. Hypoventilation result in hypoxia and hypercapnia. Hypoxia and hypercapnia cause precapillary vasoconstriction lead to pulmonary hypertension finally result in cor pulmonale.

Hypoxia also lead to increase production of erythropoietin resulting in polycytemia.

We can detected hypoxia by formation of cyanosis.

Chronic bronchitis also lead to emphysema by chronic inflammation which cause production of proteolytic enzyme that damage the alveoli.

treatment for chronic brochitis is quite the same with asthmatic bronchiole

what is asthma?

Asthma bronchiole

Asthma affect 5-8% of the population. It is characterized by recurrent episodes of dyspnoea, cough usually at night, and wheeze caused by reversible airways obstruction.

The difference between asthma and COPD is that asthma is reversible bronchoconstriction.

When examine patient with astma , pulsus parodoxus may be noted.

Treatment:

1.       Stimulate sympathetic system to open the airways using B agonist.(B2 receptor)

2.       Inhibit parasympathetic systemusing anticholinergic

3.       Reduce inflammation using glucocorticoids.

There are 2 types of astma:

1.       Allergic astma-predominatly occur to children. This results from sensitization to allergens. when there is exposure to allergen,  stimulation of IgE OCCURS. THEN IgE bind to mast cells. When there is next exposure to allergen, it will be detected by mast cells that bind to ige, reeleasing histamine. Histamine cause mucus secretion , inflammation, vascular permeability and bronchospasm and lead to narrowing of airways.

2.       Idiopathic asthma. Usually occur after 40 years old. Usually occur after infections.