PATHOPHYSIOLOGY

Etiologic Factor IPredisposing Factors Factors Gender Present Justification According to Huether and McCance (2012), incidence of Type 1 DM in gender is similar in males and females. Race Huether and McCance (2012) stated that races like non-Hispanic blacks, Hispanic/Latino, American Indians, Alaska Natives, Asian Americans, and Pacific Islanders have between 1.5 and 2.2 times the risk of whites. Family history According to Huether and McCance (2012), there are between 10% and 13% of individuals with newly diagnosed type 1 DM have a first-degree relative with type 1 DM. Age It affects people primarily after 40 years of age, as mentioned by Huether and McCance. Socioeconomic status It is more common among those lower income countries.

II-

Precipitating Factors Factors Present Justification Obesity is a risk factor because and it is the

obesity

major contributor to insulin resistance through adipokines released in adipose tissue (McCance & Huether, 2010). Physical inactivity Inactivity increases serum triglycerides ad cholesterol and decreases the HDL

Symptomatology Type 2 Diabetes Mellitus Symptoms hyperglycemia Present Justification In type 2 DM, elevated serum glucose level happens when there is insufficient insulin produced by the beta cell. The less sensitive the insulin receptor, the higher concentration of glucose is retained in the bloodstream (Porth, 2010). Polydipsia Because of elevated serum glucose levels, water is osmotically attracted from body cells, resulting in intracellular dehydration and stimulation of thirst in hypothalamus (Huether & McCance, 2008). Polyuria Hyperglycemia acts as an osmotic diuretic; the amount of glucose filtered by the glomeruli of the kidneys exceed that which can be reabsorbed by the renal tubules; glucosuria results, accompanied by large amounts water lost in the urine (Huether & McCance, 2008). polyphagia Depletion of cellular stores of carbohydrates, fat, and protein results in cellular starvation

and a corresponding increase in hunger (Huether & McCance, 2008). Recurrent infection Growth of microorganisms is stimulated by increased glucose levels; impaired blood supply hinders healing (McCance & Huether, 2010). Our patient had undergone gram staining culture and sensitivity in her sputum and urine. The result was both had the presence of Staphylococcus aureus and Candida infections. Moreover, the patient had a cellulitis in the left leg and the wound was gram stained, cultured, and being treated by different antibiotics. It also had S. aureus and candidal infections. Genital pruritus Hyperglycemia and glycosuria favor fungal growth; candidal infections, resulting in pruritus (McCance & Huether, 2010). Visual changes Blurred vision occurs as water balance in the eye fluctuates because of elevated blood glucose levels; diabetic retinopathy is another cause of visual loss (McCance & Huether, 2010). Our patient had already undergone extracapsular cataract extraction in the left eye last 2010. She said that months or years after she was diagnosed with type 2 DM, her vision fluctuates until there was luring on her left eye. Paresthesia Paresthesias are common manifestation o diabetic neuropathies (Jameson, 2010).

Fatigue and lethargy

Metabolic changes result in poor use of food products, contributing to lethargy and fatigue (McCance & Huether, 2010).

Dyslipidemia

Dyslipidemic because of the mild lypolysis.

Myelodysplastic Syndromes Symptoms Pallor, dyspnea, fatigue Present Justification Pallor, dyspnea, and fatigue are initial symptoms of anemia because one problem of MDS is insufficient production of RBCs Skin infection Leukopenia is also one the problem f MDS due to immature blast cells. Prolonged wound healing Platelets are the responsible for clotting. If there is low amount of platelet, prolonged wound healing ise xpected

SCHEMATIC DIAGRAM Predisposing Factors: Age Gender Race Family history Genetic predisposition Precipitating Factors: Obesity Physical inactivity

Decrease beta cell mass & beta cell dysfunction

Presence of adipokines, increase serum FFA, intracellular deposits of triglycerides and cholesterol, and inflammatory cytokines

Relative insulin deficiency

Insulin resistance

Increase in insulin counterregulatory hormones

Insulin receptors are less sensitive to insulin

Glucose cannot pass through the cell

B
High serum glucose level

hyperglycemia

Stimulates beta cells to produce more insulin

Less sensitivity to insulin receptors

Increase HGT result

High blood glucose level

Pancreatic beta cells compensate by increasing the insulin output

Increase insulin level in the plasma

hyperinsulinemia

B
Over workload of the pancreatic beta cells

Beta cell exhaustion

Beta cell dysfunction

Impaired insulin secretion

hypoinsulinemia

Mild lypolysis (fat breakdown)

Glycogenolysis in the liver (breakdown of glycogen)

Protein breakdown

Liberation of FFA and glycerol

Gluconeogenesis (formation of glucose)

Amino acid formation

B1

B2

B1
Increased lipid synthesis in hepatocytes (steatosis)

B2
Chronic hyperglycemia

Abnormal liver function tests

Nonalcoholic fatty liver disease Depletion of cellular stores of carbohydrates, fats, and protein dyslipidemia Osmotic diuretic High osmotic pressure in the plasma

Increased triglycerides and LDL and decreased HDL

Cellular starvation atherogenesis

High filtration of glucose

Intracellular dehydration

Polyphagia If not treated: Coronary artery disease Stroke Peripheral vascular disease

Polydipsia

Treatment: Lipid lowering agent Antihypertensives atherectomy

Genital pruritus, recurrent infections

Glucosuria

Antibiotics

Polyuria GOOD PROGNOSIS

FAIR PROGNOSIS

C
Microvascular diseases

Hyperperfusion in retinal plasma flow and activation of PKC

Aldose reductase catalyzes glucose to sorbitol

Increased advanced glycosylation end product

Aldose reductase catalyzes glucose to sorbitol

Vascular cell proliferation, enhanced contractility, and increased permeability

Sorbitol is converted into fructose by sorbitol dehydrogenase

Inactivation of nitric oxide

Sorbitol interferes with ion pumps

Vasoconstriction Increased intracellular osmotic pressure

Capillary endothelial cell is damaged

Decreased nerve blood flow in vaso nervorum

Capillary occlusion

Cell injury in epithelial cells

Demyelination of Schwann cells

C1

C2

C3

Paresthesia, tingling sensation, absence of ankle reflexes, numbness

C1
Visual changes, complete blindness Retinal ischemia Treatment: Aldose reductase inhibitor Treatment: Regular eye examination Laser photocoagulation Limit valsalva maneuver Aspirin therapy Glycemic and blood pressure control If not treated: Diabetic retinopathy

C2

If not treated: cataract

Extracapsular cataract extraction

GOOD PROGNOSIS

C3

GOOD PROGNOSIS Treatment: Vitamin B12 and folate supplement Antidepressants/anticonvulsants Adequate salt intake Avoidance of dehydration and diuretics If not treated: Diabetic neuropathy

GOOD PROGNOSIS

D
Hyperfiltration and hypoperfusion in the kidneys

Increased afferent arteriole dilatation

Increase intraglomerular pressure

Greater mesangial matrix production

D3

Renal vasodilation occurs

4
proteinuria Increased GFR and protein excretion First 5 years Diabetic nephrosclerosis Hardening of the nephrons Glomerular hypertrophy and mesangial volume expansion Sodium deficit and volume depletion Increased sodium excretion

D1

D2

D1
5-10 years Microalbuminuria/ proteinuria Begins to excrete small amounts of albumin

D2
Juxtaglomerular apparatus secretes renin

D2

Progression increased in intraglomerular pressure

Renin converts Angiotensinogen to Ang I

Increases glomerular capillary permeability

ACE converts Ang I to Ang II in the lungs

Treatment: ACE inhibitor

hypoproteinemia

Excretion of big amount of albumin

Ang II stimulates adrenal gland to secrete aldosterone

Treatment: ARBS

Decreased plasma colloid osmotic pressure

Nephron injury

D3

Aldosterone increases water retention and increase BP

4
Edema, anasarca Water retention in tissues Mild decrease in GFR 60-89mL/min

Treatment: Decrease OFI

: Stage 2 CKD

D2

D1

D1

Increase creatinine and urea

Increased serum creatinine and urea concentration

Glomerular capillary hypertension

Increased glomerular permeability and filtration

proteinuria

Increased tubular protein reabsorption

Tubulointerstitial fibrosis

Renal scarring

Increase loss of nephrons

Systemic hypertension

Stage 3 CKD

Moderate decrease in GFR 30-59mL/min

Increase cardiac output

E3

More kidney damage

Impaired renal synthesis of calcitriol

Increase afterload and increase heart workload

Impaired erythropoietin production

Decreased calcium intestinal absorption

Hypertrophy of the myocardium

Decreased production of RBCs

Serum phosphate binds to calcium

E2

Pallor, fatigue, weakness, dyspnea

Anemia

hypocalcemia

Blood transfusion, oxygen administration

E1

E1
Stimulates parathyroid gland to produce PTH

Hyperparathyroidism

Vitamin D deficiency

hypercalcemia Treatment: Vitamin D replacement Phosphorus supplements Sunlight exposure If not treated: osteomalacia

Treatment: Hyperphosphatemia control Al OH

If not treated: Vascular calcification (mitral, tricuspid, and aortic sclerosis)

FAIR PROGNOSIS

GOOD PROGNOSIS

Congestive heart failure

BAD PROGNOSIS

Myelodysplastic syndrome

F
Serum viscosity

Familial monosomy 7 abnormality Decreased tissue perfusion

Refractory anemia (RA)

RA with excess blasts

Refractory cytopenia with multilineage dysplasia

RA with ringed sideroblasts

MDSUnclassified

Decrease blood flow to the kidneys

RAAS activation

erythrocytopenia

leukopenia

thrombocytopenia

High blood pressure

Anemia, fatigue dyspnea, pallor

Infection

Decreased clotting factor, increased bleeding

vasoconstriction

Treatment: Blood transfusion O2 therapy

Treatment: antibiotics

Increase cardiac output Treatment: antihemorrhagic

F
Increase afterload and increase heart workload

Hypertrophy of the myocardium

Decreased myocardial contractility

E2

Ventricular remodelling

Increase preload

Troponin I (+)

Myocardial infarction

Stretched the myocardium and constrict the arteries

E3
Moderate hypertension Chest pain / angina pectoris

F
Hypoxia of the myocardium Treatment: Vasodilator nitrates

STAGE 4 CKD

Severe decrease of GFR 15-29ml/min

Decreased contractility

Kussmaul respiration

metabolic acidosis

Treatment: NaHCO3

Left ventricular hypertrophy

STAGE 5 ESRD

Kidney failure; GFR of <15mL/min

Increased residual of blood in the left ventricle

Regurgitation of blood into the lungs Treatment: Dialysis Kidney transplant Supportive therapy If not treated: Uremia Pericarditis CVA or MI

crackles

Venous pulmonary congestion

BAD PROGNOSIS FAIR PROGNOSIS Death

Pulmonary hypertension

Pulmonary edema

Treatment: O2 administration Diuretics Decrease OFI and sodium intake

If not treated: Shock and suffocation

BAD PROGNOSIS

GOOD PROGNOSIS

DEATH

Narrative Form of Schematic Diagram

Diabetes mellitus (DM) is caused by various factors. Some books may indicate that DM is idiopathic but specifically, DM results from a severe, absolute lack of insulin caused by loss of beta cells in the pancreas; wherein fact, beta cells are the one responsible for the release of insulin, only hormone know to have a direct effect in lowering blood glucose levels. Diabetes mellitus has two types: type 1 DM and type 2 DM. Type 1 DM is previously known as insulin-dependent DM because and type 2 DM is non-insulindependent DM, however, these terms are obsolete because many individuals of type 2 DM eventually require insulin treatment for control of glycemia (Jameson, 2010). In line with this, patient AU was diagnosed with type 2 DM, accordingly, we will explain the pathophysiology of this type of DM. Type 2 DM is a heterogeneous condition that describes the presence of hyperglycemia in association with relative insulin deficiency (Porth, 2010). There are various factors that contribute to type 2 DM. One factor that has a great cause on a person to have type 2 DM is obesity. Obesity is a major contributor to insulin resistance through several mechanisms like presence of adipokines, increases serum free fatty acids (FFA), intracellular deposits of triglycerides and cholesterol, and inflammatory cytokines will make the insulin resistant. Insulin resistance is defined as suboptimal response of insulin-sensitive tissues to insulin. It is an abnormality of either the insulin molecules, down-regulation of insulin receptors, decrease or abnormal activation of postreceptor kinases, and alteration of glucose transporter. So, when a person eats food that is rich in carbohydrates, it breaks down and turns into glucose and moves into the bloodstream. The body detects that there is an increase in blood glucose level; therefore, insulin is stimulated to control the glucose level in the plasma. However, in patients with type 2 DM the insulin doesnt bind to insulin receptors in the cell. The insulin receptors are less sensitive, though the pancreas continues to produce some insulin, but it is not enough to meet the bodys needs. When the body cells are less

sensitive to insulin, glucose cannot enter into the cell causing high blood glucose level (hyperglycemia). Beta cells secrete more insulin to compensate the hyperglycemia. As time goes by, insulin receptors continue to be less sensitive and more glucose is retained in the plasma. Therefore, more insulin are produced by the beta cells leading to hyperinsulinemia, and so on and so forth. In due to over workload of the pancreas specifically the beta cells in producing insulin, insulin response will decline due to beta cell exhaustion and dysfunction. Impaired insulin secretion or relative insulin deficiency is the result of beta cell dysfunction. On the other hand, genetic predisposition is also a risk factor for type 2 DM. according to some studies; there are incidences of genetically beta cell dysfunction and decrease beta cell mass. And because of this, insulin counterregulatory hormones (catecholamines, cortisol, growth hormone, and glucocorticoid) will increase. Consequently, when the insulin secretion is impaired it cannot function well on its job in maintaining the homeostasis of glycogen and glucose. Deficiency of insulin causes a mild lypolysis, glycogenolysis, and protein breakdown. The products are essential in gluconeogenesis that will result in high blood glucose level formation the more the patient will be hyperglycemic. Originally, insulin is the one responsible for glycogen synthesis and decreases gluconeogenesis, increase triglyceride synthesis and inhibits adipose cell lipase, and decreases protein breakdown. But when there is impaired insulin secretion the insulin cannot perform its function well, therefore, fats, protein, and glycogen will catabolize. In the adipose tissue, there is only a mild lypolysis because the body has still relative amount of insulin left. Moreover, free fatty acids and glycerol will now circulate freely in the bloodstream and contributes to the formation of more glucose. Increase in FFA will lead also to increase lipid synthesis in hepatocytes. This lipid storage in the liver may lead to nonalcoholic fatty liver diseases and abnormal liver function test. This is also responsible for dyslipidemia and can cause macrovascular diseases (Jameson, 2010). Lipid lowering agents like statins and antihypertensives. By the same token, there will be glycogenolysis in the liver and more glucose is producedchronic hyperglycemia is

expected. And also, same will happen in proteins; proteins catabolize and amino acid is formed and this may contribute in the production of glucose. As what have mentioned above, chronic hyperglycemia will happen if the body will continue to produce more glucose when the body cannot compensate its high sugar level. In line with this, the initial manifestation of type 2 DM will occur. The classical symptoms are polyphagia, polydipsia, and polyuria. Polyphagia happens when the cell depletes energy or food source and results in cellular starvation and increase hunger. On the other hand, polydipsia is an intracellular dehydration due to the attraction of water into the plasma, consequently, due to high blood glucose level. Thus, intracellular dehydration stimulates the thirst mechanism of hypothalamus. Polyuria occurs when there is too much water is being secreted in the urine because the amount of glucose filtered by the glomeruli of the kidney exceeds that which can be reabsorbed by the renal tubules. Glucosuria is present and may also contribute to fungal growth called genital pruritus or any infections due to attraction of microorganisms on a high sugar level environment. Furthermore, Huether and McCance (2012) stated that chronic complications of DM are associated with metabolic alterations, primarily hyperglycemia. Strict blood control of blood glucose significantly reduces complications. If there is a macrovascular complication of DM, there is also microvascular diseases primarily due to hyperglycemiadiabetic retinopathy, neuropathy, and nephropathy. Firstly, DM retinopathy is caused due to retinal ischemia resulting from blood vessel changes and RBC aggregation. Hyperglycemia causes hyperperfusion in retinal plasma flow and vascular pericyte loss because of the activation of protein kinase C (PKC) that contributes to vascular cell proliferation, enhanced contractility, and increased permeability. Because of this, the capillary endothelial cell is damage with loss of tight junctions, capillary occlusion that will lead to retinal ischemia and may lead to visual changes and complete blindness. By the same token, polyol pathway also has also a central role in initiating diabetic cataract formation. The enzyme aldose reductase catalyzes the reduction of glucose to sorbitol through a polyol pathway. That is why aldose reductase inhibitor are given to patients to inhibit the enzyme during the

catalyzation. Sorbitol is slowly converted into fructose by the enzyme sorbitol dehydrogenase. Osmotic stress in the lens caused by sorbitol accumulation induces apoptosis in lens of epithelial cells leading to the development of cataract. Usual management for persons with cataract is cataract surgery or extracapsular cataract extraction. Secondly, hyperglycemia increases ICF sorbitol (due to polyol pathway) that can contribute to nerve edema. Increases advanced glycosylation end-products (AGEs) formation can cause inactivation of nitric oxide, a potent vasodilator that will result to vasoconstriction, decrease nerve blood flow in the vaso nervorum, and ischemic injury and demyelination of Schwann cells. Nerve edema and demyelination of Schwann cells may alter sensorimotor function. This alteration in the nerve function is called diabetic neuropathy. Paresthesia, tingling sensation, numbness, and absence of ankle reflexes are the manifestations of DM neuropathy. Lastly, DM nephropathy is a chronic complication that causes DM patients to have chronic kidney disease (CKD) or eventually will lead to end-stage renal disease (ESRD). With DM nephropathy, early glomerular hemodynamic changes include hyperfiltration and hyperperfusion which result in microalbuminuria. Increase afferent arteriole dilation due to a dysfunction of basic and constrictive autoregulatory inflammatory response contributes to increase intraglomerular pressure exacerbated by systemic hypertension which is associated to greater mesangial matrix production. Renal vasodilation may first occur and there will be an increase in GFR and increase protein excretion. During the first 5 years of DM, thickening of the glomerular basement membrane, glomerular hypertrophy, and mesangial volume expansion occur as the GFR returns to normal. There are some instances that the nephrons will harden due to excessive use and will develop diabetic nephrosclerosis. After 510 years, 40% of individuals begin to excrete small amounts of albumin in the urine. Microalbuminuria is defined as 30300 mg/dL in a 24-hr collection or 30300 g/mg creatinine in a spot collection. Macroalbuminuria progresses over the next 10 years in some individuals. Once macroalbuminuria is present, there is a steady decline in GFR, and 50% of individuals reach ESRD in 710 years. Hypoproteinemia will result to increase albumin

excretion. Normally, protein increases plasma colloid osmotic pressure; however, due to protein excretion water will congest into tissues and will lead to edema and maybe anasarca. Once macroalbuminuria develops, blood pressure slightly rises and the pathologic changes are likely irreversible. During hyperfiltration, large amount of sodium will also be filtered and excreted through urine; sodium deficit and volume depletion will stimulate the juxtaglomerular apparatus to secrete renin. Renin will now convert the angiotensinogen from the liver to angiotensinogen I. As angiotensin I flow into the lungs, an enzyme cleaves of the structure of angiotensin I and will convert it into angiotensin II. This enzyme is called angiotensin-converting enzyme. Angiotensin II is a potent vasoconstrictor and promotes high blood pressure. Other function of angiotensin II is to stimulate the adrenal gland to produce aldosteronepromotes water retention, increases blood volume and increases blood pressure. This activation from stimulation of renin to the production of aldosterone is called renin angiotensin aldosterone system. In patients with DM, hypertension will increase the vascular resistance result to the progression of intraglomerular pressure and exacerbate the glomerular capillary permeability adding more injury into nephrons. Prevention of the RAAS activation is the important intervention to prevent further damage to kidneys. ACE inhibitor, ARBS, Ca channel blocker, aldosterone inhibitor, and decrease OFI are some of the treatment regimens to prevent hypertension and water retention. Stage 2 CKD has a mild decrease in GFR of 60-89 mL/min; plasma creatinine concentration increases by a reciprocal amount; because there is no regulatory adjustment for creatinine, plasma levels continue to rise and serve as an index of changing glomerular function. As GFR declines also, urea clearance increases. As the glomerular pressure continues to increase, proteins are still permeable due to hyperfiltration. There will be an increase in tubular protein reabsorption and will further bought fibrosis to tubulointerstitium. Increase losses of nephrons are prominent. There is a hypothesis that surviving nephrons are able to compensate the loss of other nephrons by hyperfunction in their rates of filtration, reabsorption, secretion and

excretion. However, the continued loss of functioning nephrons and the adaptive hyperfiltration can add insult to injury. As the kidney damage progresses, nephrons continue to injure and there will be a moderate decrease of GFR of 30-59 mL/min (Stage 3 CKD). The kidneys now will not be able to produce erythropoietin and the productions of RBCs are reduced. Patients with CKD are prone to anemia. Pallor, fatigue and weakness are the initial manifestations and may have dyspnea due to impaired gas exchange. Supposedly, the hemoglobin carries the oxygen molecule for tissue perfusion and carries carbon dioxide for gas exchange in the lungs. Moreover, damage to the kidneys can also impair the synthesis of calcitriol. Calcitriol is a hormone responsible for calcium absorption in the intestines. If there is decrease intestinal absorption of calcium, the serum calcium level also decreases. To compensate for the low amount of calcium in the blood, it will stimulate the parathyroid gland to produce parathormone (PTH). PTH is the one responsible in increasing serum calcium level and stimulation of calcitriol. But, due to impairment of calcitriol, the PTH will retain in the bloodstream leading to more complication like hyperparathyroidism. Hypercalcemia is caused by excessive production of PTH. Intake of phosphorus-riched foods is needed because, physiologically, calcium is inversely proportional to phosphorus. An increase of either of those two electrolytes will be a reduction of the other, and vice versa. If these are not treated, complications like vascular calcifications will be prone to your patient. In line with this, our patients echocardiography impression shows aortic, mitral, and tricuspid sclerosis. Sclerosis is the hardening of a soft tissue and maybe due to calcification of serum calcium. As mentioned above, damage of the kidneys result to impairment of calcitriol or Vitamin D. Vitamin D and phosphorus supplements and sunlight exposure are the treatment for vitamin D deficiency. Osteomalacia is one of the complications if not treated immediately. In addition, more kidney damage will result to moderate hypertension and severe decrease of GFR will rapidly to occur. GFR of 15-29mL/min indicates the 4th stage of

CKD. One complication of severe decrease in GFR is metabolic acidosis. Progression of kidney failure will lead to the last stage of CKD, the end-stage renal disease where uremia, pericarditis, azotemia, other cardiovascular disorders are present and slowly the patient will meet its death. Dialysis and kidney transplant are the management for ESRD. In addition, chronic hyperglycemia also makes the blood more viscous. Serum viscosity may lead to poor tissue perfusion to all organs especially the kidneys. The RAAS will be activated and increase vascular resistance is the product of its activation. Vasoconstriction may increase cardiac output, increase the afterload, and increase heart workload. Hypertrophy of the myocardium will result due to its workload until it decreases its myocardial contractility. Normally, the heart remodels as a compensatory mechanism to increase workloadmyocardial contraction will increase as well as its preload. Pathologically, our patient had a positive Troponin I and indicates myocardial infarction. Therefore, increase contraction will stretched the myocardium and constrict the coronary arteries. Hypoxia in the myocardium will happen and thus, decreasing its normal contractility. The chamber especially the left ventricles was hypertrophied and it cannot pump the whole blood towards the systemic body. Left ventricular hypertrophy will occur and there will be a minimal or increased residual of blood in the left ventricles. Because of this, the ventricle cannot pump the whole blood and some amount of blood will regurgitate back to the lungs. The regurgitation of blood is easy on her case because the patient had already calcified leaflets or valves called sclerosis. Therefore, there will be a venous pulmonary congestion with the presence of crackles in the lungs. The congestion in the lungs will lead to pulmonary edema and because of increased pressure; there will be also a pulmonary hypertension. Medications and other treatment regimen should be intervened immediately. Oxygen therapy and diuretics should be rendered and decrease OFI and sodium intake should be strictly followed. Shock and suffocation will be the major complication when not treated and may impend to death.