Block E Flashcards
functions of kidneys
*-regulation of water and inorganic ion balance
-removal of metabolic waste products from blood and excretion in urine
-removal of foreign chemicals in the blood and excretion in urine
-gluconeogenisis
how many nephron in the kidneys
2.5million in the 2
nephron functional components
tubular component and vascular component
what does glomerular filtrate do
drains into bowman’s space and then into proximal convolutes tubule
how do endothelium allow small molecules through
they have pores
what does podocytes having a negative charge do
it along with the basement membrane stops proteins getting through into tubular fluid
what does JGA do
helps regulate renal blood flow, GFR and also indirectly modulates sodium balance and systemic BP
how do the kidneys reduce renal pressure
intrarenal redistribution of pressure and increased absorption of salt and water
what does a decreased pressure in renal arterioles and sympathetic activity lead to
renin and angiotensin II production
what does angiotensin II affect in the kidneys
causes direct constriction of renal arterioles. stimulation of aldosterone synthesis- sodium absorption and increase in intravascular blood volume
what is the principal factor controlling angiotensin II levels
renin release
decreased circulating volume stimulates renin release via
decreased BP, decreased salt, decreased renal perfusion pressure
what does aldosterone stimulate
sodium reabsorption and potassium excretion by the renal tubule
how does aldosterone exert indirect negative feedback on RAAS
by increasing ECV and lowering plasma (K+)
pharmacologic treatment of cardiovascular disease
directs, sympatholytics, calcium channel blockers, direct-acting vasodilators
classification of diuretics
all indirectly prevent the re-absorption of water in kidneys
loop diuretics- furosemide supplemented with spironolactone or amiloride
thiazides- bendroflumethiazide
potassium sparing diuretics- not acting directly on sodium channels
loop diuretics mechanism of action
inhibiting the Na/K/2cl co-transporter
thiazide diuretics mechanism of action
inhibit the sodium-chloride transporter in the distal tubule, because this transporter only reabsorbs 5% of filtered sodium these diuretics are less efficacious than loop in producing diuresis and natriuresis
liver function
-major role in protein, carbohydrate and lipid homeostasis
-stores glycogen, vitamins and iron
-contains an extensive reticuloendothelial system for the synthesis and breakdown of blood cells
-liver cells metabolise, detoxify and excrete both endogenous and exogenous compounds
how are liver diseases identified
liver function tests (LFTs), complete blood count, CT scans, MRIs, ultrasounds, liver biopsy
how are liver diseases managed
limiting alcohol, maintaining healthy weight, drinking more water
how are liver diseases treated
hepatitis- antiviral drugs
liver inflammation- steroids
blood pressure medication
antibiotics
how is hepatitis A spread
contact with contaminated food or water, symptoms may clear up without treatment, recovery a few weeks
how is hepatitis B spread
can be acute or chronic, spread through bodily fluids, is treatable but no cure
how is hepatitis C spread
can be acute or chronic, spread through contact with blood of someone with hepatitis C, often doesn’t cause symptoms in early stage but can lead to permanent liver damage
what is hepatitis D
serious form of hepatitis that only develops in people with hepatitis B
how is hepatitis E spread
by drinking contaminated water, generally clears up on its own in a few weeks without any lasting complications
treating hepatitis
interferons- don’t directly kill viral or cancerous cells, they boost the immune system response stimulating T cells and other immune system cells to attack
anti-viral drugs- ombitsdvir with paritaprevir and ritonavir
sofosbuvir- inhibits the hepatitis C virus NS5B protein
fatty liver disease
alcohol fatty liver disease, caused by heavy alcohol consumption
non-alcohol fatty liver disease, caused by unknown
what happens if fatty liver diseases are left unmanaged
both types can cause liver damage, leading to cirrhosis and liver failure. diet and other lifestyle changes can often improve symptoms and reduce risk of complications
pioglitazone
improves the sensitivity of hepatic tissue to insulin. they are synthetic ligands for PPARs, they alter the transcription of genes, influencing carbohydrate and lipid metabolism- resulting in changed amounts of protein synthesis and therefore metabolic changes
autoimmune hepatisis
causes immune system to attack liver, causing inflammation. left untreated can lead to cirrhosis and liver failure
primary biliary cirrhosis
results from damage to the bile ducts in liver, causing build up of bile. PBC can lead to cirrhosis and liver failure
primary sclerosing cholangtis
infammatoru condition that causes gradual damage to bile ducts. they eventually become blocked, causing bile to build up in liver which can lead to cirrhosis or liver failure
prednisolone
increases the concentration of neutrophils; decreases T&B lymphocytes, monocytes, eosinophils and basophils. decrease in cytokine release, including decrease in IL-2 and TNF alpha
azathioprine (AZA)
immunosuppressive agent that acts through its effects as an antagonist of purine metabolism, resulting in the inhibition of DNA, RNA and protein synthesis
liver cancers
first develop in liver. if cancer starts elsewhere then spreads to liver it’d called secondary liver cancer.
most common liver cancer= heptocellular carcinoma, tends to develop as several small spots of cancer in liver but can start as a single tumour also
how are liver cancers treated
surgery, chemotherapy and pharmacotherapy
mechanism of action of immune checkpoint inhibitors
two signals are required to initiate the activation of T cells. first signal involves the binding of a MHC to a TCR on T-cells. second signal arises with the binding of the APC ligands CD80 or CD86 to CD28 on T cells
what is cholestasis
impairment of bile formation and/or bile flow, which may clinically present with fatigue, pruritus, dark urine, pale stools and in its most overt form jaundice and signs of fat soluble vitamin deficiencies
cholesterol synthesis
synthesised primarily in the liver, occurs in the cytoplasm and ER. the HMG-CoA reductase reaction is rate-limiting
functions of cholesterol
cell membranes, sex hormones, hormones released by the adrenal glands, production of bile acids
dangers of high cholesterol levels
atherosclerosis- increased coronary heart disease risk -> heart attack, angina
-stroke
-peripheral vascular disease
statins mechanism of action
inhibit an early rate and limiting step in cholesterol biosynthesis, inhibiting hepatic cholesterol synthesis results in increased expression of the LDL receptor gene. Decreased free cholesterol causes membrane-bound regulatory proteins to be cleaved and translocated to the nucleus to bind the sterol responsive element of the LDL receptor gene. This enhances transcription and increases the synthesis of LDL receptors
It also reduces the degradation of LDL receptors
what are statins
competitive inhibitors of HMG-CoA reductase, decreased cholesterol synthesis, increased expression of the LDL receptor gene.
reduced LDL levels
documented in reducing fatal and nonfatal CHD events, strokes and total mortality
statins effects on triglycerides and lipoprotein levels
-Decrease triglycerides in hypertriglyceridemic-> 35-45%
-Increase HDL-C
->Normal patients: 5-10%
->Low patients: 15-20%
-Decrease LDL-C ->20-55%
-Non-lipid lowering effects
->Endothelial function (Enhances production of nitric oxide)
->Anti-inflammatory
->Reduce venous thromboembolic events- 43%
averse effects of statins
Hepatotoxicity
-Elevated hepatic transaminase values
-One case of liver failure per million person-years of use
Myopathy
-One death per million prescriptions caused by rhabdomyolysis
